1. A compound of Formula (I-I):

or a pharmaceutically acceptable salt thereof;

wherein:

t is 1 or 2;

R⁷ is hydrogen or methyl, or when - is a double bond, R⁷ is absent;

R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R⁹ is hydrogen or substituted or unsubstituted alkyl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^lla, R^llb, R^15a, R^15b, R^16a, R^16b, R^17a, R^17b, R^18a, R^18b, R^19a, or R^19b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^lla and R^llb, R^15a and R^15b, R^16a and R^16b, R^17a and R^17b, and R^18a and R^18b are joined to form an oxo (=0) group; each of R^5a R^5b R⁸ and R¹³ is each independently hydrogen, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^a1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -C(=0)N(R^a1)₂, -0C(=0)R^a1, - 0C(=0)0R^A1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, - SC(=0)SR^A1, -SC(=0)N(R^A1)₂,-NHC(=0)R^A1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S-S(=0)₂0R^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, - S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

or R and R are joined to form an oxo (=0) group, wherein when R and R are joined to form an oxo (=0) group, R³ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and

wherein at least one of R^5a R^5b R⁸ and R¹³ must be ethyl, substituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -N(R^A1),-CN(R^A1)₂, -

wherein R⁸ and R¹³ cannot both be methyl; wherein - represents a single or double bond, provided if a double bond is present in Ring B, then one of R^6a or R^6b and R⁷ is absent.

2. The compound of claim 1, wherein R^15a and R^15b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^m,- wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

3. The compound of claim 1 or 2, wherein R^15a and R^15b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -0R^D1,-0C(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is

independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

4. The compound of any one of claim 1-3, wherein R^15a and R^15b is each independently hydrogen, substituted or unsubstituted alkyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

5. The compound of any one of claim 1-4, wherein R^15a and R^15b are both hydrogen.

6. The compound of any one of claim 1-5, wherein R^15a and R^15b is each independently hydrogen or substituted or unsubstituted alkyl.

7. The compound of any one of claim 1-6, wherein each of R^15a and R^15b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or -OH.

8. The compound of any one of claim 1-7, wherein R^15a or R^15b is -CH₃, -CH₂CH₃, -OH, - OCH₃, or -CH(CH₃)₂.

9. The compound of any one of claim 1-8, wherein R^16a or R^16b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

10. The compound of any one of claim 1-9, wherein R^16a or R^16b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

11. The compound of any one of claim 1-10, wherein R^16a or R^16b is each independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

12. The compound of any one of claim 1-11, wherein R^16a and R^16b are both hydrogen.

13. The compound of any one of claim 1-12, wherein R^16a and R^16b is each independently hydrogen or substituted or unsubstituted alkyl.

14. The compound of any one of claim 1-13, wherein each of R^16a and R^16b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or -OH.

15. The compound of any one of claim 1-14, wherein R^16a or R^16b is -CH₃, -CH₂CH₃, -OH, - OCH₃, or -CH(CH₃)₂.

16. The compound of any one of claim 1-15, wherein R^17a or R^17b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

17. The compound of any one of claim 1-16, wherein R^17a or R^17b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -0R^D1,-0C(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

18. The compound of any one of claim 1-17, wherein R^17a or R^17b is each independently hydrogen, substituted or unsubstituted alkyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

19. The compound of any one of claim 1-18, wherein R^17a and R^17b are both hydrogen.

20. The compound of any one of claim 1-19, wherein R^17a and R^17b is each independently hydrogen or substituted or unsubstituted alkyl.

21. The compound of any one of claim 1-20, wherein each of R^17a and R^17b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or -OH.

22. The compound of any one of claim 1-21, wherein R^17a or R^17b is -CH₃, -CH₂CH₃, -OH, - OCH₃, or -CH(CH₃)₂.

23. The compound of any one of claim 1-22, wherein R is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

24. The compound of any one of claim 1-23, wherein R is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -0R^D1,-0C(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

25. The compound of any one of claim 1-24, wherein R is each independently hydrogen, substituted or unsubstituted alkyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

26. The compound of any one of claim 1-25, wherein R and R are both hydrogen.

27. The compound of any one of claim 1-26, wherein R and R is each independently hydrogen or substituted or unsubstituted alkyl.

28. The compound of any one of claim 1-27, wherein each of R and R is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or -OH.

29. The compound of any one of claim 1-28, wherein R^18a or R^18b is -CH₃, -CH₂CH₃, -OH, - OCH₃, or -CH(CH₃)₂.

30. The compound of any one of claim 1-29, wherein R^19a or R^19b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

31. The compound of any one of claim 1-30, wherein R^19a or R^19b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

32. The compound of any one of claim 1-31, wherein R^19a or R^19b is each independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

33. The compound of any one of claim 1-32, wherein R^19a and R^19b are both hydrogen.

34. The compound of any one of claim 1-33, wherein R^19a and R^19b is each independently hydrogen or substituted or unsubstituted alkyl.

35. The compound of any one of claim 1-34, wherein each of R^19a and R^19b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or -OH.

36. The compound of any one of claim 1-35, wherein R^19a or R^19b is -CH₃, -CH₂CH₃, -OH, - OCH₃, or -CH(CH₃)₂.

37. The compound of any one of claim 1-36, wherein R⁷ is hydrogen in the cis position.

38. The compound of any one of claim 1-37, wherein R⁷ is hydrogen in the trans position.

39. The compound of any one of claim 1-38, wherein R⁷ is methyl in the cis position.

40. The compound of any one of claim 1-39, wherein R⁷ is methyl in the trans position.

41. The compound of any one of claim 1-40, wherein t is 1.

42. The compound of any one of claim 1-41, wherein t is 2.

43. The compound of any one of claim 1-42, wherein R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

44. The compound of any one of claim 1-43, wherein R³ is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

45. The compound of any one of claim 1-44, wherein R³ is substituted or unsubstituted alkyl.

46. The compound of any one of claim 1-45, wherein R³ is hydrogen.

47. The compound of any one of claim 1-46, wherein R³ is substituted alkyl.

48. The compound of any one of claim 1-47, wherein R³ is unsubstituted alkyl.

49. The compound of any one of claim 1-48, wherein R³ is methyl.

50. The compound of any one of claim 1-49, wherein R⁹ is hydrogen.

51. The compound of any one of claim 1-50, wherein R⁹ is substituted alkyl.

52. The compound of any one of claim 1-51, wherein R⁹ is unsubstituted alkyl.

53. The compound of any one of claim 1-52, wherein R⁹ is methyl.

54. The compound of any one of claim 1-53, wherein R⁹ is -OCH₃.

55. The compound of any one of claim 1-54, wherein R⁹ is ethyl.

56. The compound of any one of claim 1-55, wherein R^6a and R^6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

57. The compound of any one of claim 1-56, wherein R^6a and R^6b is independently hydrogen or substituted or unsubstituted alkyl.

58. The compound of any one of claim 1-57, wherein R^6a and R^6b is independently hydrogen or substituted alkyl.

59. The compound of any one of claim 1-58, wherein R^6a and R^6b is independently hydrogen or unsubstituted alkyl.

60. The compound of any one of claim 1-59, wherein both R^6a and R^6b are hydrogen.

61. The compound of any one of claim 1-60, wherein R^6a is halo or alkyl and R^6b is hydrogen.

62. The compound of any one of claim 1-61, wherein R^6a and R^6b are both halo.

63. The compound of any one of claim 1-62, wherein R^6a and R^6b are both alkyl.

64. The compound of any one of claim 1-63, wherein R^6a and R^6b are joined to form an oxo group.

65. The compound of any one of claim 1-67, wherein R^lla or R^llb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

66. The compound of any one of claim 1-65, wherein R^lla or R^llb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

67. The compound of any one of claim 1-66, wherein R^lla or R^llb is each independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

68. The compound of any one of claim 1-67, wherein R^lla and R^llb are both hydrogen.

69. The compound of any one of claim 1-68, wherein R^lla and R^llb is each independently hydrogen or substituted or unsubstituted alkyl.

70. The compound of any one of claim 1-69, wherein R⁸ or R¹³ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -OR^A1, - SR^A1, -N(R^a1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -C(=0)N(R^a1)₂, -OC(=0)R^a1, - OC(=0)OR^A1, -OC(=0)SR^a1, or -OC(=0)N(R^A1)₂, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

71. The compound of any one of claim 1-70, wherein R⁸ or R¹³ is substituted or unsubstituted alkyl, -C(0)R^A1, -C(=0)N(R^A1)₂, -OC(=0)R^A1, or -OC(=0)OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

72. The compound of any one of claim 1-70, wherein R⁸ or R¹³ is -C(0)R^A1, wherein R^A1 is substituted alkyl.

73. The compound of claim 72 wherein the alkyl is substituted with a heteroaryl.

74. The compound of claim 72, wherein the alkyl is substituted with a 5 membered heteroaryl.

75. The compound of any one of claim 1-74, wherein R^5a and R^5b are each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^A1, -OC(=0)R^A1, or - OC(=0)OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

76. The compound of any one of claim 1-74, wherein R^5a and R^5b are each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, - OR^A1, -N(R^a1)₂, -N(R^a1), -CN(R^a1)₂, -C(0)R^a1, -OC(=0)R^a1, or -OC(=0)OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

77. The compound of any one of claim 1-74, wherein R^5a and R^5b are each hydrogen.

78. The compound of claim 1, wherein the compound is of Formula (I-Ia) or Formula (I-

Iab):

or a pharmaceutically acceptable salt thereof;

wherein:

R¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and

n is 0, 1, 2, or 3.

79. The compound of claim 78, wherein the compound is of Formula (I-Ib) or Formula (I-

Ibb)

or a pharmaceutically acceptable salt thereof.

80. The compound of claim 78, wherein the compound is of Formula (I-Ic) or Formula (I-

Icb)

or a pharmaceutically acceptable salt thereof; R¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -N(R^A1), -0C(=0)R^A1, -0C(=0)0R^a1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, - SC(=0)0R^A1, -SC(=0)SR^a1, -SC(=0)N(R^A1)₂,-NHC(=0)R^A1, -NHC(=0)0R^a1, -

NHC(=0)SR^A1, -NHC(=0)N(R^a1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S- S(=0)₂0R^a1, -S(=0)R^A2, -S0₂R^A2, or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and

n is 0, 1, 2, or 3.

81. The compound of any one of claims 78-79, wherein R¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.

82. The compound of any one of claims 78-81, wherein R¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, - S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_3-4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or

optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R is independently hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

n or e is 0, 1, 2, 3, 4, or 5.

83. The compound of any one of claim 78-82, wherein R¹ is

wherein each instance of R₂₀ is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, - S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_3-4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R is independently hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R^GA groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

n or e is 0, 1, 2, 3, 4, or 5.

84. The compound of claim 1, wherein the compound is of Formula (I-Id) or Formula (I-Idb)

wherein R_l0 is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano;

or a pharmaceutically acceptable salt thereof.

85. The compound of claim 1, wherein the compound is of Formula (I-Ie) or Formula (I-Ieb)

wherein e is 0, 1, 2 or 3;

p is 0, 1, or 3;

each R₅ is independently halogen, alkyl, hydroxyl, or cyano; or a pharmaceutically acceptable salt thereof.

86. The compound of claim 1, wherein the compound is of Formula (I-If) or Formula (I-Ifb)

wherein R_l0 is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano;

or a pharmaceutically acceptable salt thereof.

87. The compound of claim 1, wherein the compound is of Formula (I-Ig) or Formula (I-Igb)

wherein and each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^GA, - C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring;

u is 0, 1, or 2; or a pharmaceutically acceptable salt thereof.

88. The compound of claim 1, wherein the compound is of Formula (I-Ih) or Formula (I-Ihb)

wherein each R_l0 is independently halogen, alkyl, hydroxyl, or cyano; and m is 0, 1, 2 or 3; or a pharmaceutically acceptable salt thereof. 89. The compound of claim 1, wherein the compound is of Formula (I-Ii) or Formula (I-Iib)

wherein each X is independently -C(R^N)-, -C(R^N)₂-, -0-, -S-, -N-, or N(Rⁿ)- wherein

R^N is independently hydrogen, substituted or unsubstituted Cl -6 alkyl, C(=0)R^GA, - C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring; n is 0, 1, 2, or 3;

or a pharmaceutically acceptable salt thereof.

90. A compound of claim 1, wherein the compound is of Formula (I-Ik) or Formula (I-Ikb)

or a pharmaceutically acceptable salt thereof;

wherein s is 0, 1, or 2; and R¹² is -N(R^ab)₂, -OR^ab , wherein each R^ab is independently H, substituted or unsubstituted alkyl, -S0₂(R¹⁵), -C(0)R¹⁵, wherein R¹⁵ is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycl, or substituted or unsubstituted cycloalkane.

91. A compound of Formula (I-II):

or a pharmaceutically acceptable salt thereof;

wherein:

R⁷⁷ is hydrogen or methyl, or when - is a double bond, R⁷ is absent;;

r23

is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R²⁹ is hydrogen or substituted or unsubstituted alkyl;

each of R^26a and R^26b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^26a and R^26b are joined to form an oxo (=0) group;

each of R^21a, R^21b, R^25a, R^25b, R^36a, R^36b, R^27a, R^27b, R^29a, or R^29b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^21a and R^21b, R^25a and R^25b, R^36a and R^36b, R^27a and R^27b, and R^29a and R^29b are joined to form an oxo (=0) group;

each of R^55a R^55b, R^33a, and R^33b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -

S(=0)₂OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; wherein - represents a single or double bond, provided if a double bond is present in Ring B, then one of R^26a or R^26b is absent, and provided if a single bond is present in Ring B, then the hydrogen at C5 is in the alpha or beta position.

92. The compound of claim 91, wherein R^25a and R^25b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, - OR^D1,-OC(=0)R^D1, -NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

93. The compound of claim 91 or 92, wherein R^25a and R^25b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -0R^D1,-0C(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is

independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

94. The compound of any one of claim 91-93, wherein R^25a and R^25b is each independently hydrogen, substituted or unsubstituted alkyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

95. The compound of any one of claim 91-94, wherein R^25a and R^25b are both hydrogen.

96. The compound of any one of claim 91-95, wherein R^25a and R^25b is each independently hydrogen or substituted or unsubstituted alkyl.

97. The compound of any one of claim 91-96, wherein each of R^25a and R^25b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or -OH.

98. The compound of any one of claim 91-97, wherein R^25a or R^25b is -CH₃, -CH₂CH₃, -OH, - OCHs, or -CH(CH₃)₂.

99. The compound of any one of claim 91-98, wherein R^36a or R^36b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

100. The compound of any one of claim 97-99, wherein R^36a or R^36b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

101. The compound of any one of claim 91-100, wherein R^36a or R^36b is each independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

102. The compound of any one of claim 91-101, wherein R^36a and R^36b are both hydrogen.

103. The compound of any one of claim 91-102, wherein R^36a and R^36b is each independently hydrogen or substituted or unsubstituted alkyl.

104. The compound of any one of claim 91-103, wherein each of R^36a and R^36b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

105. The compound of any one of claim 91-104, wherein R^36a or R^36b is -CH₃, -CH₂CH₃, - OH, -OCHs, or -CH(CH₃)₂.

106. The compound of any one of claim 91-105, wherein R^27a or R^27b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

107. The compound of any one of claim 106, wherein R^27a or R^27b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

108. The compound of any one of claim 91-107, wherein R^27a or R^27b is each independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

109. The compound of any one of claim 91-108, wherein R^27a and R^27b are both hydrogen.

110. The compound of any one of claim 91-109, wherein R^27a and R^27b is each independently hydrogen or substituted or unsubstituted alkyl.

111. The compound of any one of claim 91-110, wherein each of R^27a and R^27b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

112. The compound of any one of claim 91-111, wherein R^27a or R^27b is -CH₃, -CH₂CH₃, - OH, -OCHs, or -CH(CH₃)₂.

113. The compound of any one of claim 91-112, wherein R^29a or R^29b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

114. The compound of any one of claim 91-113, wherein R^29a or R^29b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -0R^D1,-0C(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

115. The compound of any one of claim 91-114, wherein R^29a or R^29b is each independently hydrogen, substituted or unsubstituted alkyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

116. The compound of any one of claim 91-115, wherein R^29a and R^29b are both hydrogen.

117. The compound of any one of claim 91-116, wherein R^29a and R^29b is each independently hydrogen or substituted or unsubstituted alkyl.

118. The compound of any one of claim 91-117, wherein each of R^29a and R^29b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

119. The compound of any one of claim 91-118, wherein R^29a or R^29b is -CH₃, -CH₂CH₃, - OH, -OCHs, or -CH(CH₃)₂.

120. The compound of any one of claim 91-119, wherein R^21a or R^21b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

121. The compound of any one of claim 91-120, wherein R^21a or R^21b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

122. The compound of any one of claim 91-121, wherein R^21a or R^21b is each independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

123. The compound of any one of claim 91-122, wherein R^21a and R^21b are both hydrogen.

124. The compound of any one of claim 91-123, wherein R^21a and R^21b is each independently hydrogen or substituted or unsubstituted alkyl.

125. The compound of any one of claim 91-124, wherein each of R^21a and R^21b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

126. The compound of any one of claim 91-125, wherein R^21a or R^21b is -CH₃, -CH₂CH₃, - OH, -OCHs, or -CH(CH₃)₂.

127. The compound of any one of claim 91-126, wherein R⁷⁷ is hydrogen in the cis position.

128. The compound of any one of claim 91-127, wherein R⁷⁷ is hydrogen in the trans position.

129. The compound of any one of claim 91-128, wherein R⁷⁷ is methyl in the cis position.

130. The compound of any one of claim 91-129, wherein R⁷⁷ is methyl in the trans position.

131. The compound of any one of claim 91-130, wherein R²³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

132. The compound of any one of claim 91-131, wherein R²³ is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

133. The compound of any one of claim 91-132, wherein R²³ is substituted or unsubstituted alkyl.

134. The compound of any one of claim 91-133, wherein R²³ is hydrogen.

135. The compound of any one of claim 91-134, wherein R²³ is substituted alkyl.

136. The compound of any one of claim 91-135, wherein R²³ is unsubstituted alkyl.

137. The compound of any one of claim 91-136, wherein R²³ is methyl.

138. The compound of any one of claim 91-137, wherein R²⁹ is hydrogen.

139. The compound of any one of claim 91-138, wherein R²⁹ is substituted alkyl.

140. The compound of any one of claim 91-139, wherein R²⁹ is unsubstituted alkyl.

141. The compound of any one of claim 91-140, wherein R²⁹ is methyl.

142. The compound of any one of claim 91-141, wherein R²⁹ is -OCH₃.

143. The compound of any one of claim 91-142 wherein R²⁹ is ethyl.

144. The compound of any one of claim 91-143, wherein R^26a and R^26b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

145. The compound of any one of claim 91-144, wherein R^26a and R^26b is independently hydrogen or substituted or unsubstituted alkyl.

146. The compound of any one of claim 91-145, wherein R^26a and R^26b is independently hydrogen or substituted alkyl.

147. The compound of any one of claim 91-146, wherein R^26a and R^26b is independently hydrogen or unsubstituted alkyl.

148. The compound of any one of claim 91-147, wherein both R^26a and R^26b are hydrogen.

149. The compound of any one of claim 91-148, wherein R^26a is halo or alkyl and R^26b is hydrogen.

150. The compound of any one of claim 91-149, wherein R^26a and R^26b are both halo.

151. The compound of any one of claim 91-150, wherein R^26a and R^26b are both alkyl.

152. The compound of any one of claim 91-151, wherein R^26a and R^26b are joined to form an oxo group.

153. The compound of any one of claim 91-152, wherein R^55a or R^55b is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -OR^A1, -SR^a1, -N(R^a1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -C(=0)N(R^a1)₂, -OC(=0)R^a1, - OC(=0)OR^A1, -OC(=0)SR^a1, or -OC(=0)N(R^A1)₂, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

154. The compound of any one of claim 91-153, wherein R^55a or R^55b is substituted or unsubstituted alkyl, -C(0)R^A1, -C(=0)N(R^A1)₂, -0C(=0)R^A1, or -0C(=0)0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

155. The compound of any one of claim 91-154, wherein R^55a or R^55b is -C(0)R^A1, - C(=0)N(R^A1)₂, wherein R^A1 is substituted alkyl.

156. The compound of claim 155 wherein the alkyl is substituted with a heteroaryl.

157. The compound of claim 155, wherein the alkyl is substituted with a 5 membered heteroaryl.

158. The compound of any one of claim 91-157, wherein R^33a andR^33b are each

independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -N(R^A1),-CN(R^A1)₂, - C(0)R^A1, -0C(=0)R^a1, or -0C(=0)0R^a1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

159. The compound of any one of claim 91-158, wherein R^33a andR^33b are each

independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^A1, -N(R^A1)₂, -N(R^A1), -CN(R^A1)₂, -C(0)R^A1, -0C(=0)R^A1, or - 0C(=0)0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

160. The compound of any one of claim 91-159, wherein R^33a andR^33b are each hydrogen.

161. A compound of claim 91, wherein the compound is of Formula (I-IIa) or Formula (I-

Ilab)

R31 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and

d is 0, 1, 2, or 3; v is 0, 1, 2, or 3;

or a pharmaceutically acceptable salt thereof.

162. A compound of claim 91, wherein the compound is of Formula (I-IIb) or Formula (I-

Ilbb)

Ilbb)

wherein R_{3 I} is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and

v is 0, 1, 2, or 3;

or a pharmaceutically acceptable salt thereof.

163. The compound of any one of claims 161-163, wherein R³¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.

164. The compound of any one of claims 162-163, wherein R³¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, - S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_{3 -}4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R^GA is independently hydrogen, substituted or unsubstituted

Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

n or e is 0, 1, 2, 3, 4, or 5.

165. The compound of any one of claim 162-164, wherein R³¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, - S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_3-4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or

optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R is independently hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

e is 0, 1, 2, 3, 4, or 5.

166. The compound of claim 91, wherein the compound is of Formula (I-IId) or Formula (I-

Ildb)

wherein v is 0, 1, 2, or 3; R_l0 is independently halogen, alkyl, hydroxyl, or cyano; or a pharmaceutically acceptable salt thereof.

167. The compound of claim 91, wherein the compound is of Formula (I-IIe) or Formula (I-

Ileb)

wherein n is 0, 1, 2 or 3;

v is 0, 1, 2, or 3;

p is 0, 1, or 3;

each R₅ is independently halogen, alkyl, hydroxyl, or cyano;

or a pharmaceutically acceptable salt thereof.

168. The compound of claim 91, wherein the compound is of Formula (I-IIf) or Formula (I-

Ilfb)

wherein v is 0, 1, 2, or 3; R_l0 is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano;

or a pharmaceutically acceptable salt thereof.

169. The compound of claim 91, wherein the compound is of Formula (I-IIg) or Formula (I- Ilgb)

wherein each v is 0, 1, 2, or 3 and X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)OR^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring;

or a pharmaceutically acceptable salt thereof.

170. The compound of claim 91, wherein the compound is of Formula (I-IIh) or Formula (I-

Ilhb)

wherein each v is 0, 1, 2, or 3;

Rio is independently halogen, alkyl, hydroxyl, or cyano; and

m is 0, 1, 2 or 3;

or a pharmaceutically acceptable salt thereof.

171. The compound of claim 91, wherein the compound is of Formula (I-IIi) or Formula (I-

Ilib)

wherein v is 0, 1, 2, or 3; each X is independently -C(R^N)-, -C(R^N)₂-, -0-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Cl -6 alkyl, C(=0)R^ga, -C(=0)OR^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring;

or a pharmaceutically acceptable salt thereof.

172. A pharmaceutical composition comprising a compound of any one of claims 1-171 or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

173. A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of any one of claims 1-172 or a pharmaceutically acceptable salt thereof.

174. The method of claim 173, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive disorder, a disorder of memory and/or cognition, a movement disorder, a personality disorder, autism spectrum disorder, pain, traumatic brain injury, a vascular disease, a substance abuse disorder and/or withdrawal syndrome, tinnitus, or status epilepticus.

175. The method of claim 173, wherein the CNS-related disorder is depression.

176. The method of claim 173, wherein the CNS-related disorder is postpartum depression.

177. The method of claim 173, wherein the CNS-related disorder is major depressive disorder.

178. The method of claim 177, wherein the major depressive disorder is moderate major depressive disorder.

179. The method of claim 177, wherein the major depressive disorder is severe major depressive disorder.

180. The compound of any one of claims 1-171, wherein R³ is methoxymethyl or

ethoxym ethyl.

181. The compound of any one of claims 1-171, wherein when R⁸ or R¹³ is -C(0)CH₃, then R³ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

182. The compound of claim 91, wherein the compound is of Formula (I-IIj)

or a pharmaceutically acceptable salt thereof;

wherein s is 0, 1, or 2; and R¹² is -N(R^ab)₂, -OR^ab , wherein each R^ab is independently H, substituted or unsubstituted alkyl, -S0₂(R¹⁵), -C(0)R¹⁵, wherein R¹⁵ is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycl, or substituted or unsubstituted cycloalkane.

183. The compound of any one of claims 1-91, wherein R⁸ or R¹³ is -C(0)R^A1, - C(=0)N(R^ai)₂ wherein R^A1 is substituted alkyl.

184. The compound of any one of claims 1-91, wherein R⁸ and R¹³ are joined to form an oxo (=0) group

185. A compound of Formula (P-I):

or a pharmaceutically acceptable salt thereof;

wherein:

t is 1;

n is 0, 1 or 2; R¹⁹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted C₂-C₆ alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl;

R⁵ is hydrogen or methyl, or when - is a double bond, R⁵ is absent;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

R¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -N(R^A1), -OC(=0)R^A1, -OC(=0)OR^A1, -OC(=0)SR^A1,

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

each of R^la, R^lb, R^2a, R^2b, R^2aa, R^2ab, R^3a, R^3b, R^4a, R^4b, R^7a, R^7b, R^lla, R^llb, R^12a, or

R^12b, is independently hydrogen, halogen, cyano, nitro, azido, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form a substituted or unsubstituted heterocyclic ring; or any one of R^2a and R^2b, R^3a and R^3b, R^4a and R^4b, R^7a and R^7b, R^lla and R^llb, and R^12a and R^12b are joined to form an oxo (=0) group;

wherein at least one of R^la, R^lb, R^2a, R^2b, R^2aa, R^2ab, R^3a, R^3b, R^4a or R^4b is hydroxyl; each of R^15a, R^15b, R^16a and R^16b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1,

S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and wherein when n is 0, t is 1, R¹⁹ is methyl, R⁵ is hydrogen, R^3a is hydroxyl, Ring B has a double bond, and R^6a, R^6b, R^la, R^lb, R^2a, R^2b, R^2aa, R^2ab, R^3b, R^4a, R^4b, R^7a, R^7b, R^lla, R^llb, R^{I :I} _anc[ R^{l b} _{are eac}h hydrogen, then R¹ is not methyl;

wherein - represents a single or double bond, provided if a double bond is present in Ring B, then one of R^6a or R^6b and R⁵ is absent.

185. A compound of Formula (II-I) wherein R¹⁹ is hydrogen.

186. A compound of Formula (II-P):

or a pharmaceutically acceptable salt thereof;

wherein the variables are defined as recited in Formula (P-I); wherein at least one of R^la, R^lb, R^2a, R^2b, R^3a, or R^3b, is hydroxyl.

187. The compound of claim 185 or 186, wherein R^2a and R^2b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 188. The compound of any one of claims 185-187, wherein R^2a and R^2b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -0R^D1,-0C(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or sub stituted or unsub stituted heteroaryl .

189. The compound of any one of claims 185-188, wherein R^2a and R^2b is each independently hydrogen, substituted or unsubstituted alkyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

190. The compound of any one of claims 185-189, wherein R^2a and R^2b are both hydrogen.

191. The compound of any one of claims 185-190, wherein R^2a and R^2b is each independently hydrogen or substituted or unsubstituted alkyl.

192. The compound of any one of claims 185-191, wherein each of R^2a and R^2b is

independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

193. The compound of any one of claims 189-192, wherein R^2a and R^2b is -CH₃, -CH₂CH₃, - OH, -OCH₃, or -CH(CH₃)₂.

194. The compound of any one of claims 189-193 wherein R^2aa and R^2ab is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

195. The compound of any one of claims 185-194, wherein R^2aa and R^2ab is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

196 The compound of any one of claims 185-195, wherein R^2aa and R^2ab is each

independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, - N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

197. The compound of any one of claims 185-196, wherein R^2aa and R^2ab are both hydrogen.

198. The compound of any one of claims 185-197, wherein R^2aa and R^2ab is each

independently hydrogen or substituted or unsubstituted alkyl.

199. The compound of any one of claims 185-198, wherein each of R^2aa and R^2ab is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

200. The compound of any one of claims 185-199, wherein R^2aa and R^2ab is -CH₃, -CH₂CH₃, - OH, -OCH₃, or -CH(CH₃)₂.

201. The compound of any one of claims 185-200, wherein R^la and R^lb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

202. The compound of any one of claims 185-201, wherein R^la and R^lb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

203. The compound of any one of claims 185-202, wherein R^la and R^lb is each independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

204. The compound of any one of claims 185-203, wherein R^la and R^lb are both hydrogen.

205. The compound of any one of claims 185-204, wherein R^la and R^lb is each independently hydrogen or substituted or unsubstituted alkyl.

206. The compound of any one of claims 185-205, wherein each of R^la and R^lb is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

207. The compound of any one of claims 185-206, wherein R^la and R^lb is -C¾, -CH₂CH₃, - OH, -OCH₃, or -CH(CH₃)₂.

208. The compound of any one of claims 185-207 wherein R^4a or R^4b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

209. The compound of any one of claims 185-208, wherein R^4a and R^4b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

210. The compound of any one of claims 185-209, wherein R^4a and R^4b is each independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

211. The compound of any one of claims 185-210, wherein R^4a and R^4b are both hydrogen.

212. The compound of any one of claims 185-211, wherein R^4a and R^4b is each independently hydrogen or substituted or unsubstituted alkyl.

213. The compound of any one of claims 185-212, wherein each of R^4a and R^4b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

214. The compound of any one of claims 185-213, wherein R^4a and R^4b is -CH₃, -CH₂CH₃, - OH, -OCH₃, or -CH(CH₃)₂.

215. The compound of any one of claims 185-214, wherein R^lla or R^llb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

216. The compound of any one of claims 185-215, wherein R^lla or R^llb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

217. The compound of any one of claims 185-216, wherein R^lla or R^llb is each independently hydrogen, substituted or unsubstituted alkyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or - NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

218. The compound of any one of claims 185-217, wherein R^lla or R^llb are both hydrogen.

219. The compound of any one of claims 185-218, wherein R^lla or R^llb is each independently hydrogen or substituted or unsubstituted alkyl.

220. The compound of any one of claims 185-219, wherein each of R^lla or R^llb is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

221. The compound of any one of claims 185-220, wherein R^lla or R^llb is -CH₃, -CH2CH3, - OH, -OCH3, or -CH(CH₃)₂.

222. The compound of any one of claims 185-221, wherein R^lla and R^llb can together form oxo.

223. The compound of any one of claims 185-222, wherein R^15a or R^15b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

224. The compound of any one of claims 185-223, wherein R^16a or R^16b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

225. The compound of any one of claims 185-224, wherein R^7a or R ^b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

226. The compound of any one of claims 185-225, wherein R^7a and R^7b are both hydrogen.

227. The compound of any one of claims 185-226, wherein R^7a and R^7b is each independently hydrogen or substituted or unsubstituted alkyl.

228. The compound of any one of claims 185-227, wherein each of R^7a and R^7b is

independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH.

229. The compound of any one of claims 185-228, wherein R^7a or R ^b is -C¾, -CH₂CH₃, - OH, -OCH₃, or -CH(CH₃)₂.

230. The compound of any one of claims 185-229, wherein R⁵ is hydrogen in the cis position, relative to the C19 position.

231. The compound of any one of claims 185-230, wherein R⁵ is hydrogen in the trans position, relative to the C 19 position.

232. The compound of any one of claims 185-231, wherein R⁵ is methyl in the cis position, relative to the C19 position.

233. The compound of any one of claims 185-232, wherein R⁵ is methyl in the trans position, relative to the C19 position.

234. The compound of any one of claims 185-233, wherein n is 1.

235. The compound of any one of claims 185-234, wherein n is 2.

236. The compound of any one of claims 185-235, wherein R^3a or R^3b is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

237. The compound of any one of claims 185-236, wherein R^3a or R^3b is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

238. The compound of any one of claims 185-237, wherein R^3a or R^3b is substituted or unsubstituted alkyl.

239. The compound of any one of claims 185-238, wherein R^3a or R^3b is hydrogen.

240. The compound of any one of claims 185-239, wherein R^3a or R^3b is substituted alkyl.

241. The compound of any one of claims 185-240, wherein R^3a or R^3b is unsubstituted alkyl.

242. The compound of any one of claims 185-241 , wherein R^3a or R^3b is methyl.

19

243. The compound of any one of claims 185-242, wherein R is ethyl.

244. The compound of any one of claims 185-243, wherein R¹⁹ is substituted alkyl

245. The compound of any one of claims 185-244, wherein R¹⁹ is unsubstituted alkyl.

246. The compound of any one of claims 185-245, wherein R¹⁹ is substituted C₂-C₆ alkyl.

247. The compound of any one of claim 185 246, wherein R 19

is unsubstituted C₂ C₆ alkyl.

248. The compound of any one of claims 185-247, wherein R¹⁹ is substituted C₂-C₆ alkenyl

249. The compound of any one of claims 185-248, wherein R¹⁹ is unsubstituted C₂-C₆ alkenyl.

250. The compound of any one of claims 185-249, wherein R¹⁹ is substituted C₂-C₆ alkynyl.

251. The compound of any one of claims 185-250, wherein R^6a and R^6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

252. The compound of any one of claims 185-251, wherein R^6a and R^6b is independently hydrogen or substituted alkyl.

253. The compound of any one of claims 185-252, wherein both R^6a and R^6b are hydrogen.

254. The compound of any one of claims 185-253, wherein R^6a is halo or alkyl and R^6b is hydrogen.

255. The compound of any one of claims 185-254 wherein R^6a and R^6b are both halo.

256. The compound of any one of claims 185-255, wherein R^6a and R^6b are both alkyl.

257. The compound of any one of claims 185-256, wherein R^12a and R^12b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

258. The compound of any one of claims 185-257, wherein R^12a and R^12b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR^D1,-OC(=0)R^D1, -NH₂, or -N(R^D1)₂, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

259. The compound of any one of claims 185-258, wherein R^12aand R^12b is each

independently hydrogen, substituted or unsubstituted alkyl, -0R^D1,-0C(=0)R^D1, -NH₂, - N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

260. The compound of any one of claims 185-259, wherein R^12aand R^12b are both hydrogen.

261. The compound of any one of claims 185-260, wherein R^12aand R^12b is each

independently hydrogen or substituted or unsubstituted alkyl.

262. The compound of any one of claims 185-261, wherein each of R^12aand R^12b is independently hydrogen, Ci-C₆ alkyl, Ci-C₆ haloalkyl, Ci-C₆ alkoxy, Ci-C₆ alkoxyhalo, or - OH. 263. The compound of any one of claims 185-262, wherein R^12aand R^12b is -C¾, -CH2CH3,

-OH, -OCH3, or -CH(CH₃)_2.

264. The compound of any one of claims 185-263, wherein R^12aand R^12b are both hydrogen. 265. The compound of any one of claims 185-264, wherein R^12aand R^12b together form oxo.

266. The compound of any one of claims 185-265, wherein R^12aand R^12b is each

independently hydrogen or substituted or unsubstituted alkyl.

267. The compound of any one of claims 185-266, wherein Ring A is selected from the group consisting of

wherein ΆLL/' indicates where A attaches to Ring B.

268. The compound of any one of claims 185-267, wherein R¹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.

269. The compound of any one of claims 185-268, wherein R¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, -

S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_{3 -}4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, C . io substituted or unsubstituted aryl, substituted or unsubstituted 5- to 10- membered heteroaryl, or optionally two R are taken with the intervening atoms to form a substituted or unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R^GA is independently hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

e is 0, 1, 2, 3, 4, or 5 and n is 0, 1, 2, 3, 4, or 5.

270. The compound of any one of claims 185-269, wherein R¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, - S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_{3 -}4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, C . io substituted or unsubstituted aryl, substituted or unsubstituted 5- to 10- membered heteroaryl, or optionally two R are taken with the intervening atoms to form a substituted or unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R is independently hydrogen, substituted or unsubstituted

Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

e is 0, 1, 2, 3, 4, or 5 and n is 0, 1, 2, 3, 4, or 5.

271. The compound of claim 185, wherein the compound of Formula (II-I) is of Formula (Ilia), (II-Iab), or (II-Iac):

lab) or a pharmaceutically acceptable salt thereof.

272. The compound of claim 185, wherein the compound of Formula (II-I) is of Formula (II- Ib), (II-Ibb), or (II-Ibc)

or a pharmaceutically acceptable salt thereof. 273. The compound of claim 185, wherein the compound of Formula (II-I) is of Formula (II-

Ic), (II-Icb), or (II-Icc)

or a pharmaceutically acceptable salt thereof. 274. The compound of claim 185, wherein the compound of Formula (II-I) is of Formula (II-

Ie), (II-Ieb), or (II-Iec)

wherein m is 0, 1, 2 or 3;

p is 0, 1, or 3; each R³² is independently halogen, alkyl, hydroxyl, or cyano;

or a pharmaceutically acceptable salt thereof.

275. The compound of claim 185, wherein the compound of Formula (II-I) is of Formula (II- Ig), (II-Igb), or (II-Igc)

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl,

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring;

or a pharmaceutically acceptable salt thereof.

276. The compound of claim 185, wherein the compound of Formula (II-I) is of Formula (II- leg), (II-Iegb), or (Il-Iegc)

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^Nis independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring;

or a pharmaceutically acceptable salt thereof.

277. The compound of claim 185, wherein the compound of Formula (II-I) is of Formula (II- Ih), (II-Ihb), or (II-Ihc)

wherein each R³⁵ is independently halogen, alkyl, hydroxyl, or cyano; and r is 0, 1, 2 or 3; or a pharmaceutically acceptable salt thereof.

278. The compound of claim 185, wherein the compound of Formula (II-I) is of Formula (II- Ii), (II-Iib), or (II-Iic)

l

wherein s is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -0-, -S-, -N-, or N(Rⁿ)- wherein R^Nis independently hydrogen, substituted or unsubstituted Cl -6 alkyl,

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring;

or a pharmaceutically acceptable salt thereof. 279. The compound of claim 186, wherein the compound of Formula (II-P) is of Formula

(II-IIa) or (Il-IIab):

Ilab) or a pharmaceutically acceptable salt thereof.

280. The compound of claim 186, wherein the compound of Formula (II-P) is of Formula

(II-IIb) or (II-IIbb)

or a pharmaceutically acceptable salt thereof.

281. The compound of claim 186, wherein the compound of Formula (II-II) is of Formula (II-IIc) or (II-IIcb)

or a pharmaceutically acceptable salt thereof.

282. The compound of claim 186, wherein the compound of Formula (II-II) is of Formula

(II-IIe) or (II-IIeb)

wherein m is 0, 1, 2 or 3;

p is 0, 1, or 3;

each R³² is independently halogen, alkyl, hydroxyl, or cyano;

or a pharmaceutically acceptable salt thereof.

283. The compound of claim 186, wherein the compound of Formula (II-P) is of Formula

(II-IIg) or (II-IIgb)

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl,

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring;

or a pharmaceutically acceptable salt thereof.

284. The compound of claim 186, wherein the compound of Formula (II-P) is of Formula

(II-IIh) or (II-IIhb)

Ilhb) wherein each R³⁵ is independently halogen, alkyl, hydroxyl, or cyano; and r is 0, 1, 2 or 3; or a pharmaceutically acceptable salt thereof.

285. The compound of claim 186, wherein the compound of Formula (II-II) is of Formula

(II-IIi) or (II-IIib)

wherein s is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^I )₂-, -0-, -S-, -N-, or N(R > N^I )- wherein R^N is independently hydrogen, substituted or unsubstituted Cl -6 alkyl, C(=0)R^ga, -C(=0)OR^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring;

or a pharmaceutically acceptable salt thereof.

286. A pharmaceutical composition comprising a compound of any one of claims 185-285 or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

287. A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of any one of claims 185-286 or a pharmaceutically acceptable salt thereof.

288. The method of claim 287, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive disorder, a disorder of memory and/or cognition, a movement disorder, a personality disorder, autism spectrum disorder, pain, traumatic brain injury, a vascular disease, a substance abuse disorder and/or withdrawal syndrome, tinnitus, or status epilepticus.

289. The method of claim 287, wherein the CNS-related disorder is depression.

290. The method of claim 287, wherein the CNS-related disorder is postpartum depression.

291. The method of claim 287, wherein the CNS-related disorder is major depressive disorder.

292. The method of claim 287, wherein the major depressive disorder is moderate major depressive disorder.

293. The method of claim 287, wherein the major depressive disorder is severe major depressive disorder.

294. A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject a compound of Formula (IP-I):

or a pharmaceutically acceptable salt thereof,

wherein

R⁵ is hydrogen or substituted or unsubstituted methyl, or when - is a double bond, R⁵ is absent;

R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R¹⁹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^la, R^lb, R^12a, R^12b, R^2a, R^2b, R^4a, R^4b, R^lla, R^llb, R^18a, and R^18b, is

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^la and R^lb, R^12a and R^12b, R^2a and R^2b, R^4a and R^4b, R^lla and R^llb, and R^18a and R^18b are joined to form an oxo (=0) group; each of R^7a, R^7b , R^7aa, and R^7bb is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, - NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^d1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^7a and R^7b and R^7aa and R^7bb are joined to form an oxo (=0) group;

each of R^16a R^16b R^17a and R^17b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or R^17a and R^17b are joined to form an oxo group; and

wherein - represents a single or double bond, provided if a double bond is present, then R⁵ and one of R^6a or R^6b are absent.

295. The method of claim 294, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive disorder, a disorder of memory and/or cognition, a movement disorder, a personality disorder, autism spectrum disorder, pain, traumatic brain injury, a vascular disease, a substance abuse disorder and/or withdrawal syndrome, tinnitus, or status epilepticus.

296. The method of claim 294 or 295, wherein the CNS-related disorder is postpartum depression. 297. The method of any one of claims 294-296, wherein the CNS-related disorder is major depressive disorder.

298. The method of any one of claims 294-297, wherein the CNS-related disorder is administered chronically or acutely.

299. The method of any one of claims 294-298, wherein the CNS-related disorder is administered orally, intravenously, transdermally, intranasally, or subcutaneously.

300. The method of any one of claims 294-299, wherein the CNS-related disorder is administered orally.

301. The method of any one of claims 294-300, wherein the CNS-related disorder is administered intravenously. 302. A compound of Formula (III-I):

or a pharmaceutically acceptable salt thereof,

wherein

R⁵ is hydrogen or substituted or unsubstituted methyl, or when - is a double bond, R⁵ is absent;

R³ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R¹⁹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^la, R^lb, R^12a, R^12b, R^2a, R^2b, R^4a, R^4b, R^lla, R^llb, R^18a, and R^18b, is

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^la and R^lb, R^12a and R^12b, R^2a and R^2b, R^4a and R^4b, R^lla and R^llb, and R^18a and R^18b are joined to form an oxo (=0) group;

each of R^7a, R^7b , R^7aa, and R^7bb is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, - NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^d1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^7a and R^7b and R^7aa and R^7bb are joined to form an oxo (=0) group;

each of R^16a R^16b R^17a and R^17b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or R^17a and R^17b are joined to form an oxo group; and

wherein - represents a single or double bond, provided if a double bond is present, then R⁵ and one of R^6a or R^6b are absent.

303. The compound of claim 302, wherein R^2a and R^2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, - OR^D1,-OC(=0)R^D1, -NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

304. The compound of any one claims 302-303, wherein R^lla and R^llb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

305. The compound of any one claims 302-304, wherein R^16a and R^16b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

306. The compound of any one claims 302-305, wherein R^7a, R^7b, R^7aa, and R^7bb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

307. The compound of any one claims 302-306, wherein R^6a and R^6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

308. The compound of any one claims 302-307, wherein R^12a and R^12b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

309. The compound of any one claims 302-308, wherein R^17a and R^17b is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -OR^A1, -SR^a1, -N(R^a1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -OC(=0)R^a1, -OC(=0)OR^a1, - OC(=0)SR^A1, or -OC(=0)N(R^A1)₂, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

310. The compound of any one of claims 302-309, wherein the compound is of Formula

(III-Ia)

or a pharmaceutically acceptable salt thereof. 311. The compound of any one of claims 302-310, wherein the compound is of Formula

(Ill-lb)

or a pharmaceutically acceptable salt thereof.

312. The compound of any one of claims 302-309, wherein the compound is of Formula

(III-Ic)

or a pharmaceutically acceptable salt thereof. 313. The compound of any one of claims 302-309, wherein the compound is of Formula

(Ill-Id)

or a pharmaceutically acceptable salt thereof.

314. The compound of any one of claims 302309, wherein the compound is of Formula

(Ill-Ie)

or a pharmaceutically acceptable salt thereof.

315. The compound of any one of claims 302-309, wherein the compound is of Formula (Ill-If)

or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, - 0C(=0)R^A1, -0C(=0)0R^a1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, -SC(=0)SR^a1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S-S(=0)₂0R^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, or 2.

316. The compound of any one of claims 302-309, wherein the compound is of Formula

(Ill-Ig)

or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, - OC(=0)R^A1, -OC(=0)OR^a1, -OC(=0)SR^a1, -OC(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)OR^a1, -SC(=0)SR^a1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)OR^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -OS(=0)₂OR^a1, -S-S(=0)₂R^A2, -S-S(=0)₂OR^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, 2, or 3.

317. The compound of claim 315 or 316, wherein R¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, - S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_{3 -}4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R is independently hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

e is 0, 1, 2, 3, 4, or 5.

318. The compound of claim 294, wherein the compound is of Formula (Ill-Ih)

or a pharmaceutically acceptable salt thereof,

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^Nis independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

319. The compound of claim 294, wherein the compound is of Formula (Ill-Ii) or a pharmaceutically acceptable salt thereof,

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

320. The compound of claim 315, wherein the compound is of Formula (Ill-Ij )

ij)

or a pharmaceutically acceptable salt thereof,

wherein m is 0, 1, 2 or 3; n is 0, 1, or 2; and

each R²¹ is independently halogen, alkyl, hydroxyl, or cyano.

321. The compound of claim 316, wherein the compound is of Formula (Ill-Ik)

wherein m is 0, 1, 2 or 3; n is 0, 2, or 2; and

each R , 2^Z1ⁱ is independently halogen, alkyl, hydroxyl, or cyano.

322. The compound of claim 320 or 321, wherein R²¹ is -CN.

323. The compound of any one of claims 320-322, wherein m is 1 and n is 1. 324. The compound of claim 315, wherein the compound is of Formula (III-IL)

or a pharmaceutically acceptable salt thereof. 325. The compound of any one of claims 316, wherein the compound is of Formula (III-

Im)

or a pharmaceutically acceptable salt thereof.

326. The compound of claim 294, wherein the compound is of Formula (III-In) or

Formula (III-Io)

or a pharmaceutically acceptable salt thereof,

wherein s is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -0-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Cl -6 alkyl, C(=0)R^ga, -C(=0)OR^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring. 327. The compound of any one of claims 302-326, wherein R³ is substituted or unsubstituted alkyl.

328. The compound of any one of claims 302-327, wherein R is unsubstituted alkyl.

329. The compound of any one of claims 302-328, wherein R³ is -CH_3. 330. The compound of any one of claims 302-329, wherein R¹⁹ is substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, or substituted or unsubstituted C₂-C₆ alkynyl.

331. The compound any one of claims 302-330, wherein R¹⁹ is unsubstituted Ci-C₆ alkyl.

332. The compound of any one of claims 302-331, wherein R¹⁹ is -CH_3.

333. A compound of Formula (III-II):

or a pharmaceutically acceptable salt thereof,

wherein

R⁵ is hydrogen or substituted or unsubstituted methyl, or when— is a double bond, R⁵ is absent;

R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^la, R^lb, R^12a, R^12b, R^2a, R^2b, R^4a, R^4b, R^lla, R^llb, R^18a, and R^18b, is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^la and R^lb, R^12a and R^12b, R^2a and R^2b, R^4a and R^4b, R^lla and R^llb, and R^18a and R^18b are joined to form an oxo (=0) group;

each of R^7a, R^7b , R^7aa, and R^7bb is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, - NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^d1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^7a and R^7b and R^7aa and R^7bb are joined to form an oxo (=0) group;

each of R^16a R^16b R^17a and R^17b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -SC^R^, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and wherein - represents a single or double bond, provided if a double bond is present, then R⁵ and one of R^6a or R^6b are absent.

334. The compound of claim 333, wherein R^2a and R^2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, - OR^D1,-OC(=0)R^D1, -NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

335. The compound of claim 333 or 334, wherein R^4a and R^4b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

336. The compound of any one claims 333-335, wherein R^lla and R^llb is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or R^lla and R^llb are joined together to form an oxo group.

337. The compound of any one claims 333-336, wherein R^16a and R^16b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

338. The compound of any one claims 333-337, wherein R^7a, R^7b, R^7aa, and R^7bb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or any of R^7a and R^7b or R^7aa and R^7bb are joined together to form oxo (=0).

339. The compound of any one claims 333-338, wherein R^6a and R^6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

340. The compound of any one claims 333-339, wherein R^12a and R^12b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

341. The compound of any one claims 333-340, wherein R^17a and R^17b is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -OR^A1, -SR^a1, -N(R^a1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -0C(=0)R^a1, -0C(=0)0R^a1, - 0C(=0)SR^A1, or -0C(=0)N(R^A1)₂, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

342. The compound of any one of claims 333-341, wherein the compound is of Formula

(III-IIa)

or a pharmaceutically acceptable salt thereof. 343. The compound of any one of claims 333-342, wherein the compound is of Formula

(III-IIb)

or a pharmaceutically acceptable salt thereof.

344. The compound of any one of claims 333-342, wherein the compound is of Formula

(III-IIc)

or a pharmaceutically acceptable salt thereof.

345. The compound of any one of claims 333-342, wherein the compound is of Formula (III-IId)

or a pharmaceutically acceptable salt thereof.

346. The compound of any one of claims 333-342, wherein the compound is of Formula

(Ill-lie)

-lie)

or a pharmaceutically acceptable salt thereof. 347. The compound of any one of claims 333-342, wherein the compound is of Formula

(III-IIf)

or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, - 0C(=0)R^A1, -0C(=0)0R^a1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, -SC(=0)SR^a1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S-S(=0)₂0R^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, 2, or 3.

348. The compound of any one of claims 333-342, wherein the compound is of Formula

(Ill-IIg)

or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, - 0C(=0)R^A1, -0C(=0)0R^a1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, -SC(=0)SR^a1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S-S(=0)₂0R^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, 2, or 3.

349. The compound of claim 347 or 348, wherein R 1 is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, -

S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_{3 -}4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R is independently hydrogen, substituted or unsubstituted

Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

e is 0, 1, 2, 3, 4, or 5. 350. The compound of claim 294, wherein the compound is of Formula (III-IIh)

or a pharmaceutically acceptable salt thereof,

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^Nis independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)OR^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

351. The compound of claim 294, wherein the compound is of Formula (III-IIi)

or a pharmaceutically acceptable salt thereof, wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^Nis independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

352. The compound of claim 347, wherein the compound is of Formula (III-IIj)

or a pharmaceutically acceptable salt thereof,

wherein m is 0, 1, 2 or 3;

n is 0,1, or 2; and

each R²¹ is independently halogen, alkyl, hydroxyl, or cyano. 353. The compound of claim 348, wherein the compound is of Formula (Ill-Ilk)

or a pharmaceutically acceptable salt thereof; wherein m is 0, 1, 2 or 3; n is 0, 1, 2, or 3; and each R²¹ is independently halogen, alkyl, hydroxyl, or cyano.

354. The compound of claim 352 or 353, wherein R²¹ is -CN.

355. The compound of any one of claims 352-354, wherein m is 1 and n is 1.

356. The compound of claim 347, wherein the compound is of Formula (III-IIL)

or a pharmaceutically acceptable salt thereof.

357. The compound of claim 348, wherein the compound is of Formula (III-IIm)

or a pharmaceutically acceptable salt thereof.

358. The compound of claim 294, wherein the compound is of Formula (III-IIn) or Formula

(III-IIo)

or a pharmaceutically acceptable salt thereof,

wherein s is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -0-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Cl -6 alkyl,

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring. 359. The compound of any one of claims 333-358, wherein R³ is substituted or unsubstituted alkyl.

360. The compound of any one of claims 333-359, wherein R³ is unsubstituted alkyl.

361. The compound of any one of claims 333-360, wherein R³ is -CH_3. 362. A pharmaceutical composition comprising a compound of any one of claims 294-361 and a pharmaceutically acceptable excipient.

363. The compound of claim 302, wherein R^16a and R^16b or R^17a and R^17b is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted aryl.

364. A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject a compound of Formula (IV-I):

or a pharmaceutically acceptable salt thereof,

wherein

R⁵ is hydrogen or substituted or unsubstituted methyl, or when - is a double bond, R⁵ is absent;

R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R¹⁹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^la, R^lb, R^12a, R^12b, R^2a, R^2b, R^4a, R^4b, R^lla, R^llb, R^18a, and R^18b is

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^la and R^lb, R^12a and R^12b, R^2a and R^2b, R^4a and R^4b, R^lla and R^llb, and R^18a and R^18b are joined to form an oxo (=0) group;

each of R^16a R^16b R^17a and R^17b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and wherein represents a single or double bond, provided if a double bond is present, then R⁵ and one of R^6a or R^6b are absent.

365. The method of claim 364, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive disorder, a disorder of memory and/or cognition, a movement disorder, a personality disorder, autism spectrum disorder, pain, traumatic brain injury, a vascular disease, a substance abuse disorder and/or withdrawal syndrome, tinnitus, or status epilepticus.

366. The method of claim 364 or 365, wherein the CNS-related disorder is postpartum depression.

367. The method of any one of claims 364-366, wherein the CNS-related disorder is major depressive disorder. 368. The method of any one of claims 364-367, wherein the CNS-related disorder is administered chronically or acutely.

369. The method of any one of claims 364-368, wherein the CNS-related disorder is administered orally, intravenously, transdermally, intranasally, or subcutaneously.

370. The method of any one of claims 364-369, wherein the CNS-related disorder is administered orally.

371. The method of any one of claims 364-370, wherein the CNS-related disorder is administered intravenously.

372. A compound of Formula (IV-I):

or a pharmaceutically acceptable salt thereof,

wherein

R⁵ is hydrogen or substituted or unsubstituted methyl, or when - is a double bond, R⁵ is absent;

R³ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R¹⁹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^la, R^lb, R^12a, R^12b, R^2a, R^2b, R^4a, R^4b, R^lla, R^llb, R^18a, and R^18b is

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^la and R^lb, R^12a and R^12b, R^2a and R^2b, R^4a and R^4b, R^lla and R^llb, and R^18a and R^18b are joined to form an oxo (=0) group;

each of R^16a R^16b R^17a and R^17b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and wherein - represents a single or double bond, provided if a double bond is present, then R⁵ and one of R^6a or R^6b are absent.

373. The compound of claim 372, wherein R^2a and R^2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, - 0R^D1,-0C(=0)R^D1, -NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

374. The compound of claim 372 or 373, wherein R^4a and R^4b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

375. The compound of any one claims 372-374, wherein R^lla and R^llb is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

376. The compound of any one claims 372-375, wherein R^16a and R^16b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

377. The compound of any one claims 372-376, wherein R^6a and R^6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

378. The compound of any one claims 372-377, wherein R^12a and R^12b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

379. The compound of any one claims 372-378, wherein R^17a and R^17b is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -OR^A1, -SR^a1, -N(R^a1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -0C(=0)R^a1, -0C(=0)0R^a1, - 0C(=0)SR^A1, or -0C(=0)N(R^A1)₂, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

380. The compound of any one of claims 372-379, wherein the compound is of Formula

(IV-Ia)

or a pharmaceutically acceptable salt thereof.

381. The compound of any one of claims 372-380, wherein the compound is of Formula

(IV-Ib)

or a pharmaceutically acceptable salt thereof.

382. The compound of any one of claims 372-380, wherein the compound is of Formula

(IV-Ic)

or a pharmaceutically acceptable salt thereof.

383. The compound of any one of claims 372-380, wherein the compound is of Formula

(IV-Id)

or a pharmaceutically acceptable salt thereof.

384. The compound of any one of claims 372-380, wherein the compound is of Formula

(IV-Ie)

or a pharmaceutically acceptable salt thereof.

385. The compound of any one of claims 372-380, wherein the compound is of Formula

(IV-If)

or a pharmaceutically acceptable salt thereof; wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, - OC(=0)R^A1, -OC(=0)OR^a1, -OC(=0)SR^a1, -OC(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)OR^a1, -SC(=0)SR^a1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)OR^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -OS(=0)₂OR^a1, -S-S(=0)₂R^A2, -S-S(=0)₂OR^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and

n is 0, 1, 2, or 3.

386. The compound of any one of claims 372-380, wherein the compound is of Formula

(IV-Ig)

or a pharmaceutically acceptable salt thereof; wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, - OC(=0)R^A1, -OC(=0)OR^a1, -OC(=0)SR^a1, -OC(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)OR^a1, -SC(=0)SR^a1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)OR^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -OS(=0)₂OR^a1, -S-S(=0)₂R^A2, -S-S(=0)₂OR^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, 2, or 3.

387. The compound of claim 385 or 386, wherein R¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, - S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_3-4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R is independently hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

e is 0, 1, 2, 3, 4, or 5.

388. The compound of claim 364, wherein the compound is of Formula (IV-Ih)

or a pharmaceutically acceptable salt thereof;

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)OR^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

389. The compound of claim 364, wherein the compound is of Formula (IV-Ii)

or a pharmaceutically acceptable salt thereof;

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R , N^I \)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

390. The compound of claim 385, wherein the compound is of Formula (IV-Ij)

or a pharmaceutically acceptable salt thereof; wherein m is 0, 1, 2 or 3;

each R²¹ is independently halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano;

391. The compound of claim 386, wherein the compound is of Formula (IV-Ik)

or a pharmaceutically acceptable salt thereof; wherein m is 0, 1, 2 or 3;

each R²¹ is independently halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano.

392. The compound of claim 390 or 391, wherein R²¹ is -CN. 393. The compound of any one of claims 390-392, wherein m is 1 and n is 1.

394. The compound of claim 385, wherein the compound is a compound of Formula (IV-

IL)

or a pharmaceutically acceptable salt thereof.

395. The compound of claim 386, wherein the compound is a compound of Formula (IV-

Im)

or a pharmaceutically acceptable salt thereof.

396. The compound of claim 364, wherein the compound is of Formula (IV-In) or

Formula (IV-Io)

or a pharmaceutically acceptable salt thereof;

wherein s is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -0-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Cl -6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

397. The compound of any one of claims 372-396, wherein R³ is substituted or

unsubstituted alkyl.

398. The compound of any one of claims 372-397, wherein R³ is unsubstituted Ci-C₆ alkyl.

399. The compound of any one of claims 372-398, wherein R³ is -CFl·,.

400. The compound of any one of claims 372-399, wherein R¹⁹ is substituted or unsubstituted Ci C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, or substituted or unsubstituted C₂-C₆ alkynyl.

401. The compound any one of claims 372-400, wherein R¹⁹ is unsubstituted Ci-C₆ alkyl.

402. The compound of any one of claims 372-401, wherein R¹⁹ is -CH_3. 403. A compound of Formula (IV-II):

or a pharmaceutically acceptable salt thereof,

wherein

R⁵ is hydrogen or substituted or unsubstituted methyl, or when - is a double bond, R⁵ is absent;

R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^la, R^lb, R^12a, R^12b, R^2a, R^2b, R^4a, R^4b, R^lla, R^llb, R^18a, and R^18b is

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^la and R^lb, R^12a and R^12b, R^2a and R^2b, R^4a and R^4b, R^lla and R^llb, and R^18a and R^18b are joined to form an oxo (=0) group;

each of R^16a R^16b R^17a and R^17b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and wherein represents a single or double bond, provided if a double bond is present, then R⁵ and one of R^6a or R^6b are absent.

404. The compound of claim 403, wherein R^2a and R^2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, - OR^D1,-OC(=0)R^D1, -NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

405. The compound of claim 403 or 404, wherein R^4a and R^4b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

406. The compound of any one claims 403-405, wherein R^lla and R^llb is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or R^lla and R^llb are joined together to form an oxo group.

407. The compound of any one claims 403-406, wherein R^16a and R^16b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

408. The compound of any one claims 403-407, wherein R^7a, R^7b, R^7aa, and R^7bb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or any of R^7a and R^7b or R^7aa and

R?bb are joined together to form oxo (=0).

409. The compound of any one claims 403-408, wherein R^6a and R^6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl. 410. The compound of any one claims 403-409, wherein R^12a and R^12b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

411. The compound of any one claims 403-410, wherein R^17a and R^17b is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -OR^A1, -SR^a1, -N(R^a1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -OC(=0)R^a1, -OC(=0)OR^a1, - OC(=0)SR^A1, or -OC(=0)N(R^A1)₂, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

412. The compound of any one of claims 403-411, wherein the compound is a compound ofFormula (IV-IIa)

or a pharmaceutically acceptable salt thereof.

413. The compound of any one of claims 403-412, wherein the compound is a compound of F ormul a (IV -lib)

or a pharmaceutically acceptable salt thereof.

414. The compound of any one of claims 403-412, wherein the compound is a compound ofFormula (IV-IIc)

or a pharmaceutically acceptable salt thereof. 415. The compound of any one of claims 403-412, wherein the compound is a compound of F ormul a (IV -lid)

or a pharmaceutically acceptable salt thereof.

416. The compound of any one of claims 403-412, wherein the compound is a compound ofFormula (IV-IIe)

or a pharmaceutically acceptable salt thereof.

417. The compound of any one of claims 403-412, wherein the compound is a compound of Formula (IV-IIf)

or a pharmaceutically acceptable salt thereof;

wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -0C(=0)R^A1, - 0C(=0)0R^A1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, - SC(=0)SR^A1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S-S(=0)₂0R^a1, - S(=0)R^A2, -S0₂R⁴², or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and n is 0, 1, 2, or 3.

418. The compound of any one of claims 403-412, wherein the compound is a compound of Formula (IV-IIg)

or a pharmaceutically acceptable salt thereof;

wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -OC(=0)R^A1, - OC(=0)OR^A1, -OC(=0)SR^a1, -OC(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)OR^a1, - SC(=0)SR^A1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)OR^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -OS(=0)₂OR^a1, -S-S(=0)₂R^A2, -S-S(=0)₂OR^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, 2, or 3.

419. The compound of claim 417 or 418, wherein R¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, - S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_{3 -}4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R^GA is independently hydrogen, substituted or unsubstituted

Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

e is 0, 1, 2, 3, 4, or 5.

420. The compound of claim 364, wherein the compound is of Formula (IV-IIh)

or a pharmaceutically acceptable salt thereof;

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)OR^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

421. The compound of claim 364, wherein the compound is of Formula (IV-IIi)

or a pharmaceutically acceptable salt thereof;

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

422. The compound of claim 417, wherein the compound is a compound of Formula (IV- nj)

or a pharmaceutically acceptable salt thereof;

wherein m is 0, 1, 2 or 3;

n is 0, 1, 2, or 3; and

each R²¹ is independently halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano.

423. The compound of claim 418, wherein the compound is a compound of Formula (IV- Ilk)

or a pharmaceutically acceptable salt thereof;

wherein m is 0, 1, 2 or 3;

n is 0, 1, 2, or 3;

and

each R²¹ is independently halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano.

424. The compound of claim 422 or 423, wherein R²¹ is -CN.

425. The compound of any one of claims 422-424, wherein m is 1 and n is 1.

426. The compound of claim 422, wherein the compound is a compound of Formula (IV-

IIL)

or a pharmaceutically acceptable salt thereof.

427. The compound of claim 423, wherein the compound is a compound of Formula (IV- Ilm)

or a pharmaceutically acceptable salt thereof.

428. The compound of claim 364, wherein the compound is of Formula (IV-IIn) or Formula

(IV-IIo)

or a pharmaceutically acceptable salt thereof ;

wherein s is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -0-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Cl -6 alkyl,

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

429. The compound of any one of claims 403-428, wherein R³ is substituted or unsubstituted alkyl.

430. The compound of any one of claims 403-429, wherein R³ is unsubstituted Ci-C₆ alkyl.

431. The compound of any one of claims 403-430, wherein R³ is -CH_3.

432. A compound of Formula (IV-III)

or a pharmaceutically acceptable salt thereof;

wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted C, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, - OC(=0)R^A1, -OC(=0)OR^a1, -OC(=0)SR^a1, -OC(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)OR^a1, -SC(=0)SR^a1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)OR^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -OS(=0)₂OR^a1, -S-S(=0)₂R^A2, -S-S(=0)₂OR^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R¹⁹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

433. The compound of claim 432, wherein R¹ is substituted or unsubstituted Ci-C₆ alkyl.

434. The compound of claim 432 or 433, wherein R¹ is -CH_3.

435. The compound of any one of claims 432-434, wherein R¹⁹ is substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, or substituted or unsubstituted C₂-C₆ alkynyl.

436. The compound of any one of claims 432-435, wherein R¹⁹ is unsubstituted Ci-C₆ alkyl. 437. The compound of any one of claims 423-425, wherein R³ is hydrogen or unsubstituted

Ci-C₆ alkyl.

438. A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject a compound of Formula (V-I):

or a pharmaceutically acceptable salt thereof,

wherein

R⁵ is hydrogen or substituted or unsubstituted methyl, or when - is a double bond, R⁵ is absent;

R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R¹⁹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^la, R^lb, R^12a, R^12b, R^12aa, R^12bb, R^2a, R^2b, R^4a, R^4b, R^lla, R^llb, R^18a, and R^18b, is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^la and R^lb, R^12a and R^12b, R^12aa and R^12bb, R^2a and R^2b, R^4a and R^4b, R^lla and R^llb, and R^18a and R^18b are joined to form an oxo (=0) group;

each of R^7a and R^7b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or R^7a and R^7b are joined to form an oxo (=0) group;

each of R^16a R^16b R^17a and R^17b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, - N(R^A1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -0C(=0)R^a1, -0C(=0)0R^a1, -0C(=0)SR^a1, - 0C(=0)N(R^A1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, -SC(=0)SR^a1, -SC(=0)N(R^a1)₂,- NHC(=0)R^a1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, -NHC(=0)N(R^a1)₂, -0S(=0)₂R^A2, -

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and wherein - represents a single or double bond, provided if a double bond is present, then R⁵ and one of R^6a or R^6b are absent.

439. The method of claim 1, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive disorder, a disorder of memory and/or cognition, a movement disorder, a personality disorder, autism spectrum disorder, pain, traumatic brain injury, a vascular disease, a substance abuse disorder and/or withdrawal syndrome, tinnitus, or status epilepticus.

440. The method of claim 438 or 439, wherein the CNS-related disorder is postpartum depression.

441. The method of any one of claims 438-440, wherein the CNS-related disorder is major depressive disorder.

442. The method of any one of claims 438-441, wherein the CNS-related disorder is administered chronically or acutely.

443. The method of any one of claims 438-442, wherein the CNS-related disorder is administered orally, intravenously, transdermally, intranasally, or subcutaneously.

444. The method of any one of claims 438-443, wherein the CNS-related disorder is administered orally.

445. The method of any one of claims 438-444, wherein the CNS-related disorder is administered intravenously.

446. A compound of Formula (V-I):

or a pharmaceutically acceptable salt thereof,

wherein

R⁵ is hydrogen or substituted or unsubstituted methyl, or when— -is a double bond, R⁵ is absent;

R³ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R¹⁹ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl , or substituted or unsubstituted alkynyl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^la, R^lb, R^12a, R^12b, R^12aa, R^12bb, R^2a, R^2b, R^4a, R^4b, R^lla, R^llb, R^18a, and R^18b, is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^la and R^lb, R^12a and R^12b, R^12aa and R^12bb, R^2a and R^2b, R^4a and R^4b, R^lla and R^llb, and R^18a and R^18b are joined to form an oxo (=0) group;

each of R^7a and R^7b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or R^7a and R^7b are joined to form an oxo (=0) group;

each of R^16a R^16b R^17a and R^17b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and wherein represents a single or double bond, provided if a double bond is present, then R⁵ and one of R^6a or R^6b are absent.

447. The compound of claim 446, wherein R^2a and R^2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, - 0R^D1,-0C(=0)R^D1, -NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

448. The compound of claim 446 or 447, wherein R^4a and R^4b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

449. The compound of any one claims 446-448, wherein R^lla and R^llb is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

450. The compound of any one claims 446-449, wherein R^16a and R^16b is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

451. The compound of any one claims 446-450, wherein R^7a and R^7b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

452. The compound of any one claims 446-451, wherein R^6a and R^6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

453. The compound of any one claims 446-452, wherein R^12a, R^12b, R^12aa, and R^12bb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

454. The compound of any one claims 446-453, wherein R^17a and R^17b is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -OR^A1, -SR^a1, -N(R^a1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -OC(=0)R^a1, -OC(=0)OR^a1, - OC(=0)SR^A1, or -OC(=0)N(R^A1)₂, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

455. The compound of any one of claims 446-454, wherein the compound is of Formula

(V-Ia)

or a pharmaceutically acceptable salt thereof.

456. The compound of any one of claims 446-455, wherein the compound is of Formula

(V-Ib)

(V-Ib)

or a pharmaceutically acceptable salt thereof.

457. The compound of any one of claims 446-455, wherein the compound is of Formula

(V-Ic)

(V-Ic)

or a pharmaceutically acceptable salt thereof.

458. The compound of any one of claims 446-455, wherein the compound is of Formula

(V-Id)

(V-Id)

or a pharmaceutically acceptable salt thereof.

459. The compound of any one of claims 446-455, wherein the compound of Formula (V- I) is a compound of Formula (V-Ie)

(V-Ie)

or a pharmaceutically acceptable salt thereof. 460. The compound of any one of claims 446-455, wherein the compound is of Formula

(V-If)

or a pharmaceutically acceptable salt thereof;

wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -0C(=0)R^A1, - 0C(=0)0R^A1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, - SC(=0)SR^A1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S-S(=0)₂0R^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, or 2.

461. The compound of any one of claims 446-455, wherein the compound is of Formula

(V-Ig)

or a pharmaceutically acceptable salt thereof;

wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -0C(=0)R^A1, - 0C(=0)0R^A1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, - SC(=0)SR^A1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S-S(=0)₂0R^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, 2, or 3.

462. The compound of claim 460 or 461, wherein R¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)OR^ga, -OC(=0)R^ga, -OC(=0)OR^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, - S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or

optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R is independently hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

e is 0, 1, 2, 3, 4, or 5.

463. The compound of claim 438, wherein the compound of Formula (V-I) is of Formula (V-

Ih)

or a pharmaceutically acceptable salt thereof;

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

464. The compound of claim 438, wherein the compound of Formula (V-I) is of Formula (V- Ii)

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^Nis independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)OR^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

465. The compound of claim 460, wherein the compound is of Formula (V-Ij)

or a pharmaceutically acceptable salt thereof;

wherein m is 0, 1, 2 or 3; n is 0, 1, or 2; and

each R²¹ is independently halogen, alkyl, hydroxyl, or cyano.

466. The compound of claim 461, wherein the compound is of Formula (V-Ik)

(V-Ik)

or a pharmaceutically acceptable salt thereof;

wherein m is 0, 1, 2 or 3; n is 0, 1, or 2; and

each R²¹ is independently halogen, alkyl, hydroxyl, or cyano.

467. The compound of claim 465 or 466, wherein R²¹ is -CN.

468. The compound of any one of claims 465-467, wherein m is 1 and n is 1.

469. The compound of claim 460, wherein the compound is of Formula (V-IL)

or a pharmaceutically acceptable salt thereof.

470. The compound of any one of claims 461, wherein the compound is of Formula (V- Im)

or a pharmaceutically acceptable salt thereof. 471. The compound of claim 438, wherein the compound is of Formula (V-In) or Formula

(V-Io)

or a pharmaceutically acceptable salt thereof;

wherein s is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -0-, -S-, -N-, or N(Rⁿ)- wherein R^Nis independently hydrogen, substituted or unsubstituted Cl-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring. 472. The compound of any one of claims 446-471, wherein R³ is substituted or unsubstituted alkyl.

473. The compound of any one of claims 446-472, wherein R³ is unsubstituted alkyl.

474. The compound of any one of claims 446-473, wherein R³ is -CH₃.

475. The compound of any one of claims 446-474, wherein R¹⁹ is substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, or substituted or unsubstituted C₂-C₆ alkynyl.

476. The compound any one of claims 446-475, wherein R¹⁹ is unsubstituted Ci-C₆ alkyl. 477. The compound of any one of claims 446-476, wherein R¹⁹ is -CH₃.

478. A compound of Formula (V-II) :

or a pharmaceutically acceptable salt thereof,

wherein

R⁵ is hydrogen or substituted or unsubstituted methyl, or when— ^;is a double bond, R⁵ is absent;

R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

each of R^6a and R^6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R^6a and R^6b are joined to form an oxo (=0) group;

each of R^la, R^lb, R^12a, R^12b, R^12aa, R^12bb, R^2a, R^2b, R^4a, R^4b, R^lla, R^llb, R^18a, and R^18b, is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or any one of R^la and R^lb, R^12a and R^12b, R^12aa and R^12bb, R^2a and R^2b, R^4a and R^4b, R^lla and R^llb, and R^18a and R^18b are joined to form an oxo (=0) group;

each of R^7a and R^7b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^m groups are joined to form an substituted or unsubstituted heterocyclic ring; or R^7a and R^7b are joined to form an oxo (=0) group;

each of R^16a R^16b R^17a and R^17b is each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -

wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -S0₂R^A2, -C(0)R^A2, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R^A2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and wherein - represents a single or double bond, provided if a double bond is present, then R⁵ and one of R^6a or R^6b are absent.

479. The compound of claim 478, wherein R^2a and R^2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, - 0R^D1,-0C(=0)R^D1, -NH₂, -N(R^d1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

480. The compound of claim 478 or 479, wherein R^4a and R^4b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

481. The compound of any one claims 478-480, wherein R^lla and R^llb is each

independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or R^lla and R^llb are joined together to form an oxo group.

482. The compound of any one claims 478-481, wherein R^16a and R^16b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

483. The compound of any one claims 478-482, wherein R^7a and R^7b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or

unsubstituted alkynyl, -0R^D1,-0C(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or any of R^7a and R^7b or R^7aa and R^7bb are joined together to form oxo (=0).

484. The compound of any one claims 478-483, wherein R^6a and R^6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

485. The compound of any one claims 478-484, wherein R^12a, R^12b, R^12aa, and R^12bb is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR^D1,-OC(=0)R^D1, -NH₂, -N(R^D1)₂, or -NR^D1C(=0)R^D1, wherein each instance of R^m is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

486. The compound of any one claims 478-485, wherein R^17a and R^17b is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -OR^A1, -SR^a1, -N(R^a1)₂, -N(R^A1),-CN(R^A1)₂, -C(0)R^a1, -0C(=0)R^a1, -0C(=0)0R^a1, - 0C(=0)SR^A1, or -0C(=0)N(R^A1)₂, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

487. The compound of any one of claims 478-486, wherein the compound is of Formula

(V-IIa)

or a pharmaceutically acceptable salt thereof.

488. The compound of any one of claims 478-487, wherein the compound is of Formula (V-IIb)

or a pharmaceutically acceptable salt thereof. 489. The compound of any one of claims 478-487, wherein the compound is of Formula

(V-IIc)

or a pharmaceutically acceptable salt thereof.

490. The compound of any one of claims 478-487, wherein the compound is of Formula (V-IId)

or a pharmaceutically acceptable salt thereof.

491. The compound of any one of claims 478-487, wherein the compound is of Formula

(V-IIe)

(V-IIe)

or a pharmaceutically acceptable salt thereof. 492. The compound of any one of claims 478-487, wherein the compound is of Formula

(V-IIf)

or a pharmaceutically acceptable salt thereof;

wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -0C(=0)R^A1, - 0C(=0)0R^A1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, - SC(=0)SR^A1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S-S(=0)₂0R^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, 2, or 3.

493. The compound of any one of claims 478-487, wherein the compound is of Formula

(V-IIg)

or a pharmaceutically acceptable salt thereof;

wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -0C(=0)R^A1, - 0C(=0)0R^A1, -0C(=0)SR^a1, -0C(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)0R^a1, - SC(=0)SR^A1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)0R^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -0S(=0)₂0R^a1, -S-S(=0)₂R^A2, -S-S(=0)₂0R^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂0R^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

and n is 0, 1, 2, or 3.

494. The compound of claim 492 or 493, wherein R¹ is

wherein each instance of R₂o is, independently, halogen, -N0₂, -CN, -OR^GA, -N(R^GA)₂, - C(=0)R^ga, -C(=0)0R^ga, -0C(=0)R^ga, -0C(=0)0R^ga, -C(=0)N(R^ga)₂, -N(R^GA)C(=0)R^ga, -0C(=0)N(R^ga)₂, -N(R^GA)C(=0)0R^ga, -S(=0)₂R^ga, -S(=0)₂0R^ga, -0S(=0)₂R^ga, -

S(=0)₂N(R^ga)₂, or -N(R^GA)S(=0)₂R^ga; substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or

unsubstituted C_{3 -}4 carbocylyl, substituted or unsubstituted 3- to 4- membered heterocylyl, or optionally two R are taken with the intervening atoms to form a substituted or

unsubstituted 3- to 4- membered carbocyclic or heterocyclic ring;

wherein each instance of R is independently hydrogen, substituted or unsubstituted

Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring; and

e is 0, 1, 2, 3, 4, or 5. 495. The compound of claim 438, wherein the compound is of Formula (V-IIh)

or a pharmaceutically acceptable salt thereof;

wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^Nis independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring;

496. The compound of claim 438, wherein the compound is of Formula (V-IIi)

or a pharmaceutically acceptable salt thereof; wherein u is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

497. The compound of claim 492, wherein the compound is of Formula (V-IIj)

or a pharmaceutically acceptable salt thereof;

wherein m is 0, 1, 2 or 3;

n is 0, 1, or 2;

and

each R²¹ is independently halogen, alkyl, hydroxyl, or cyano.

498. The compound of claim 493, wherein the compound is of Formula (V-IIk)

or a pharmaceutically acceptable salt thereof;

wherein m is 0, 1, 2 or 3; and

each R²¹ is independently halogen, alkyl, hydroxyl, or cyano.

499. The compound of claim 497 or 498, wherein R²¹ is -CN.

500. The compound of any one of claims 497-499, wherein m is 1 and n is 1.

501. The compound of claim 492, wherein the compound is of Formula (V-IIL)

or a pharmaceutically acceptable salt thereof.

502. The compound of claim 493, wherein the compound is of Formula (V-IIm)

or a pharmaceutically acceptable salt thereof.

503. The compound of claim 438, wherein the compound is of Formula (V-IIn) or Formula

(V-IIo)

IIo)

or a pharmaceutically acceptable salt thereof ;

wherein s is 0, 1, or 2; each X is independently -C(R^N)-, -C(R^N)₂-, -0-, -S-, -N-, or N(Rⁿ)- wherein R^N is independently hydrogen, substituted or unsubstituted Cl -6 alkyl, C(=0)R^ga, -C(=0)0R^ga, -C(=0)N(R^ga)₂, -S(=0)₂R^ga, or -S(=0)₂N(R^GA)₂; and

each instance of R is independently hydrogen, substituted or unsubstituted Ci_-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted C_3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocylyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R groups are taken with the intervening atoms to form a substituted or unsubstituted heterocylyl or heteroaryl ring.

504. The compound of any one of claims 478-503, wherein R³ is substituted or unsubstituted alkyl.

505. The compound of any one of claims 478-504, wherein R³ is unsubstituted alkyl.

506. The compound of any one of claims 478-505, wherein R³ is -CH_3.

507. A compound of Formula (V-III)

or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR^A1, -SR^A1, -N(R^A1)₂, -OC(=0)R^A1, - OC(=0)OR^A1, -OC(=0)SR^a1, -OC(=0)N(R^a1)₂, -SC(=0)R^A2, -SC(=0)OR^a1, - SC(=0)SR^A1, -SC(=0)N(R^a1)₂, -NHC(=0)R^a1, -NHC(=0)OR^a1, -NHC(=0)SR^a1, - NHC(=0)N(R^A1)₂, -0S(=0)₂R^A2, -OS(=0)₂OR^a1, -S-S(=0)₂R^A2, -S-S(=0)₂OR^a1, - S(=0)R^A2, -S0₂R^A2, or -S(=0)₂OR^A1, wherein each instance of R^A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, or two R^A1 groups are joined to form an substituted or unsubstituted heterocyclic or heteroaryl ring; and R⁴² is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R³ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R¹⁹ is hydrogen or substituted or unsubstituted alkyl , substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

508. The compound of claim 502, wherein R¹ is substituted or unsubstituted Ci-C₆ alkyl.

509. The compound of claim 502 or 503, wherein R¹ is unsubstituted Ci-C₆ alkyl.

510. The compound of any one of claims 502-504, wherein R¹ is -CH3.

511. The compound of any one of claims 502-505, wherein R¹⁹ is substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, or substituted or unsubstituted C₂-C₆ alkynyl.

512. The compound of any one of claims 502-506, wherein R¹⁹ is unsubstituted Ci-C₆ alkyl.

513. The compound of any one of claims 502-507, wherein R³ is hydrogen or unsubstituted Ci-C₆ alkyl.