Attorney Docket No. MDA0075-401-PC // MDA22-068 HETEROCYCLES AS MODULATORS OF NSD ACTIVITY [001] This application claims the benefit of priority of United States provisional application no.63/377,100, filed September 26, 2022, the contents of which are incorporated by reference as if written herein in their entirety. [002] Methylation of H3K36 is a conserved epigenetic mark regulating gene transcription, alternative splicing, and DNA repair. Genes encoding H3K36 methyltransferases (KMTases) are commonly overexpressed, mutated or involved in chromosomal translocations in cancer. Molecular biology studies have demonstrated that H3K36 KMTases regulate oncogenic transcriptional programs. Nuclear receptor-binding SET domain proteins (NSD’s) are histone lysine methyltransferases (HKMTases). Their primary function is to mono- and dimethylate the ^-amine of lysine 36 of histone H3 (H3K36), utilizing S-adenosyl-L-methionine (SAM) as a methyl donor. NSD’s are key enzymes that dimethylate H3K36, which have been proposed to be a driver of multiple cancers, including multiple myeloma, lung, prostate, colorectal, liver and brain. Therefore, inhibitors of NSD’s are expected to be useful as drugs to treat a variety of cancers. [003] Provided is a new chemical scaffold previously unreported for NSD family member activity. This scaffold has the potential to offer a superior profile with respect to pharmacokinetic properties, potency, or off-target activities, resulting in an improved efficacy/tolerability profile and better patient outcomes. SUMMARY [004] Provided herein is a compound of structural Formula I: or a salt thereof, wherein: X is chosen from N and W, Y, and Z are independently chosen from N and C; R ¹ is chosen from OH and NH2; each occurrence of R ³ is chosen from hydrogen, C1-C3 alkyl, C1-C3 alkoxy, carbonyl, cyano, halogen, hydroxyl, amino, sulfonyl, sulfonylamino, aryl, heteroaryl, Attorney Docket No. MDA0075-401-PC // MDA22-068 cycloalkyl, and heterocycloalkyl, wherein aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is optionally substituted with one or two groups independently chosen from C1-C3 alkyl, C1-C3 alkoxy, cyano, halogen, hydroxyl, and amino; R ⁴ is chosen from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each of which is optionally substituted with one, two, or three groups independently chosen from C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 cycloalkoxy, C1-C6 halocycloalkoxy, carbonyl, C ₁ -C ₆ alkyl sulfonyl, halogen, and cyano; R ⁵ and R ⁶ are independently chosen from hydrogen and C1-C3 alkyl; R ⁷ and R ⁸ are independently chosen from hydrogen and C ₁ -C ₃ alkyl; k is 1, 2, or 3; R ¹⁰ is hydrogen; and n is 0 or 1. [005] Also provided herein is a compound of structural Formula I: or a salt thereof, wherein: R ¹ is chosen from OH and NH2; each occurrence of R ³ is chosen from hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, carbonyl, cyano, halogen, hydroxyl, amino, sulfonyl, sulfonylamino, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, wherein aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is optionally substituted with one or two groups independently chosen from C1-C3 alkyl, C1-C3 alkoxy, cyano, halogen, hydroxyl, and amino; R ⁴ is chosen from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each of which is optionally substituted with one, two, or three groups independently chosen from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 cycloalkoxy, C ₁ -C ₆ halocycloalkoxy, carbonyl, C ₁ -C ₆ alkyl sulfonyl, halogen, and cyano; R ⁵ and R ⁶ are independently chosen from hydrogen and C1-C3 alkyl; R ⁷ and R ⁸ are independently chosen from hydrogen and C1-C3 alkyl; Attorney Docket No. MDA0075-401-PC // MDA22-068 k is 1, 2, or 3; and n is 0 or 1. [006] Also provided herein is a pharmaceutical composition, comprising a compound recited herein, or a salt thereof, together with a pharmaceutically acceptable carrier. [007] Also provided herein is a method for treating a disease or condition that benefits from or is treatable by inhibition of nuclear SET domain-containing protein 1 or 2 (NSD1 or NSD2), comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound recited herein, or a salt thereof. [008] These and other aspects of the disclosure disclosed herein will be set forth in greater detail as the patent disclosure proceeds. DETAILED DESCRIPTION [009] As used in the present specification, the following words and phrases are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise. [010] In the following description, certain specific details are set forth in order to provide a thorough understanding of various embodiments. However, one skilled in the art will understand that the invention may be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments. Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” Further, headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed invention. [011] Reference throughout this specification to “one embodiment” or “an embodiment” or “some embodiments” or “a certain embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” or “in some embodiments” or “in a certain embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. [012] Also, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. Attorney Docket No. MDA0075-401-PC // MDA22-068 [013] When ranges of values are disclosed, and the notation “from n ₁ … to n ₂ ” or “between n ₁ … and n ₂ ” is used, where n ₁ and n ₂ are the numbers, then unless otherwise specified, this notation is intended to include the numbers themselves and the range between them. This range may be integral or continuous between and including the end values. By way of example, the range “from 2 to 6 carbons” is intended to include two, three, four, five, and six carbons, since carbons come in integer units. Compare, by way of example, the range “from 1 to 3 µM (micromolar),” which is intended to include 1 µM, 3 µM, and everything in between to any number of significant figures (e.g., 1.255 µM, 2.1 µM, 2.9999 µM, etc.). [014] The term “alkoxy”, and, interchangeably, “(alkyl)oxy”, as used herein, alone or in combination, refers to an alkyl radical attached to a molecule by oxygen. [015] The term “alkyl,” as used herein, alone or in combination, refers to a straight- chain or branched-chain saturated, hydrocarbon radical containing from 1 to 20 carbon atoms. In some embodiments, alkyl will comprise from 1 to 10 carbon atoms. In some embodiments, alkyl will comprise from 1 to 8 carbon atoms. [016] The term “alkylene,” as used herein, alone or in combination, refers to a straight chain saturated hydrocarbon attached at two or more positions, such as methylene (-CH2-), ethylene (-CH ₂ CH ₂ -), and propylene (-CH ₂ CH ₂ CH ₂ -). “Alkylene” can thus be described as – (CH2)n- with n being an positive integer. In some embodiments, n is chosen from 1 to 20. In some embodiments, n is chosen from 1 to 10. In some embodiments, n is chosen from 1 to 8. In some embodiments, n is chosen from 1 to 6. Unless otherwise specified, the term “alkyl” may include “alkylene” groups. [017] The term "amino," as used herein, alone or in combination, refers to -NH2. [018] The term "aryl," as used herein, alone or in combination, means a carbocyclic aromatic system containing one, two or three rings wherein such polycyclic ring systems are fused together. The term "aryl" embraces aromatic groups such as phenyl, naphthyl, anthracenyl, and phenanthryl. [019] The term “arylalkyl” or “aralkyl,” as used herein, alone or in combination, refers to an aryl group attached to the parent molecular moiety through an alkyl group. [020] The term “carbonyl” is art-recognized and includes such moieties as can be represented by the formula: wherein X’ is a bond or represents an oxygen, a sulfur, or a group -N-R15, and wherein R14 and R ₁₅ independently represent a hydrogen, alkyl, alkenyl, aryl, cycloalkyl, heterocycloalkyl, Attorney Docket No. MDA0075-401-PC // MDA22-068 or heteroaryl. Where X’ is an oxygen and R ₁₄ is not hydrogen, the formula represents an “ester.” Where X’ is an oxygen, and R ₁₄ is a hydrogen, the formula represents a “carboxylic acid”. Where X’ is a sulfur and R14 is not hydrogen, the formula represents a “thioester” group. Where X’ is a sulfur and R ₁₄ is a hydrogen, the formula represents a “thiocarboxylic acid” group. Where X’ is a bond, and R14 is not hydrogen, the above formula represents a “ketone” group. Where X’ is a bond, and R ₁₄ is a hydrogen, the above formula represents an “aldehyde” group. Where X’ is -N-R15, the above formula represents an “amide” group. [021] The term “cyano,” as used herein, alone or in combination, refers to -CN. [022] The term “cycloalkyl,” or, alternatively, “carbocycle,” as used herein, alone or in combination, refers to a saturated monocyclic, bicyclic or tricyclic alkyl group wherein each cyclic moiety contains from 3 to 12 carbon atom ring members. In some embodiments, cycloalkyl will comprise from 5 to 7 carbon atoms. In some embodiments, cycloalkyl will comprise a spirocyclic ring system. Examples of such cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like. “Bicyclic” and “tricyclic” as used herein are intended to include both fused ring systems, as well as the multicyclic (multicentered) saturated type. [023] The term “halo,” or “halogen,” as used herein, alone or in combination, refers to fluorine, chlorine, bromine, or iodine. [024] The term "heteroaryl," as used herein, alone or in combination, refers to a 3 to 15 membered unsaturated heteromonocyclic ring, or a fused monocyclic, bicyclic, or tricyclic ring system in which at least one of the fused rings is aromatic, which contains at least one atom chosen from N, O, and S. In some embodiments, heteroaryl will comprise from 1 to 4 heteroatoms as ring members. In some embodiments, heteroaryl will comprise from 1 to 2 heteroatoms as ring members. In some embodiments, heteroaryl will comprise from 5 to 7 atoms. The term also embraces fused polycyclic groups wherein heterocyclic rings are fused with aryl rings wherein heteroaryl rings are fused with other heteroaryl rings wherein heteroaryl rings are fused with heterocycloalkyl rings, or wherein heteroaryl rings are fused with cycloalkyl rings. Heteroaryl also includes ring systems substituted with one or more oxide (-O-) substituents, such as pyridinyl N-oxides. [025] The terms “heterocycloalkyl” and, interchangeably, “heterocycle,” as used herein, alone or in combination, each refer to a saturated, partially unsaturated, or fully unsaturated (but nonaromatic) monocyclic; saturated, partially unsaturated, or fully unsaturated (but not fully aromatic) bridged; saturated, partially unsaturated, or fully unsaturated (but not fully aromatic) bicyclic; or saturated, partially unsaturated, or fully unsaturated (but not fully Attorney Docket No. MDA0075-401-PC // MDA22-068 aromatic) tricyclic heterocyclic group containing at least one heteroatom as a ring member wherein each heteroatom may be independently chosen from nitrogen, oxygen, and sulfur. [026] In some embodiments, heterocycloalkyl will comprise a spirocyclic ring system. In some embodiments, heterocycloalkyl will comprise from 1 to 4 heteroatoms as ring members. In some embodiments, heterocycloalkyl will comprise from 1 to 2 heteroatoms as ring members. In some embodiments, heterocycloalkyl will comprise from 3 to 8 ring members in each ring. In some embodiments, heterocycloalkyl will comprise from 3 to 7 ring members in each ring. In some embodiments, heterocycloalkyl will comprise from 5 to 6 ring members in each ring. [027] “Heterocycloalkyl” and “heterocycle” are intended to include sulfones, sulfoxides, N-oxides of tertiary nitrogen ring members, such as piperidinyl N-oxide, morpholinyl-N- oxide, and carbocyclic fused and benzo fused ring systems; additionally, both terms also include systems where a heterocycle ring is fused to an aryl or heteroaryl group, as defined herein, or an additional heterocycle group. Heterocycloalkyl” and “heterocycle” also includes ring systems substituted with one or more oxo moieties, such as 2-oxoindolin-5-yl, 1-oxo-1-thiomorpholinyl and 1,1-dioxo-1-thiomorpholinyl. [028] The terms “hydroxy” and, interchangeably, “hydroxyl,” as used herein, alone or in combination, refers to -OH. [029] The term “oxo,” as used herein, alone or in combination, refers to =O. [030] The term “sulfonyl” includes the groups -S(O2)-(optionally substituted (C1- C ₆ )alkyl), -S(O ₂ )-optionally substituted aryl), -S(O ₂ )-optionally substituted heteroaryl), - S(O2)-(optionally substituted heterocycloalkyl), -S(O2)-(optionally substituted alkoxy), -S(O ₂ )-optionally substituted aryloxy), -S(O ₂ )-optionally substituted heteroaryloxy), -S(O2)-(optionally substituted heterocycloalkoxy); and -S(O2)-(optionally substituted amino). [031] The term “spirocyclic ring system” refers to a polycyclic ring system comprising two rings such that a single atom is common to both rings. [032] Any definition herein may be used in combination with any other definition to describe a composite structural group. By convention, the trailing element of any such definition is that which attaches to the parent moiety. For example, the composite group alkylamido would represent an alkyl group attached to the parent molecule through an amido group, and the term alkoxyalkyl would represent an alkoxy group attached to the parent molecule through an alkyl group. Attorney Docket No. MDA0075-401-PC // MDA22-068 [033] Asymmetric centers exist in the compounds and pharmaceutically acceptable salts thereof, disclosed herein. These centers are designated by the symbols “R” or “S,” depending on the configuration of substituents around the chiral carbon atom. It should be understood that the disclosure encompasses all stereochemical isomeric forms, including diastereomeric, enantiomeric, and epimeric forms, as well as d-isomers and 1-isomers, and mixtures thereof. Individual stereoisomers of compounds, and pharmaceutically acceptable salts thereof, can be prepared synthetically from commercially available starting materials which contain chiral centers or by preparation of mixtures of enantiomeric products followed by separation such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, direct separation of enantiomers on chiral chromatographic columns, or any other appropriate method known in the art. Starting compounds, and pharmaceutically acceptable salts thereof, of particular stereochemistry are either commercially available or can be made and resolved by techniques known in the art. Additionally, the compounds, and pharmaceutically acceptable salts thereof, disclosed herein may exist as geometric isomers. The present disclosure includes all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the appropriate mixtures thereof. [034] Additionally, the compounds disclosed herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms. [035] The term “disease” as used herein is intended to be generally synonymous, and is used interchangeably with, the terms “disorder,” “syndrome,” and “condition” (as in medical condition), in that all reflect an abnormal condition of the human or animal body or of one of its parts that impairs normal functioning, is typically manifested by distinguishing signs and symptoms, and causes the human or animal to have a reduced duration or quality of life. [036] The term "combination therapy" means the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients or in multiple, separate capsules for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein. Attorney Docket No. MDA0075-401-PC // MDA22-068 [037] The phrase "therapeutically effective" is intended to qualify the amount of active ingredients used in the treatment of a disease or disorder or on the effecting of a clinical endpoint. [038] The term “therapeutically acceptable” refers to those compounds (or salts thereof) which are suitable for use in contact with the tissues of patients without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit / risk ratio, and are effective for their intended use. [039] As used herein, the term “treat,” “treating”, or “treatment” means the administration of therapy to an individual who already manifests at least one symptom of a disease or condition or who has previously manifested at least one symptom of a disease or condition. For example, “treating” can include alleviating, abating or ameliorating a disease or condition symptoms, preventing additional symptoms, ameliorating the underlying metabolic causes of symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition. For example, the term “treating” in reference to a disorder means a reduction in severity of one or more symptoms associated with that particular disorder. Therefore, treating a disorder does not necessarily mean a reduction in severity of all symptoms associated with a disorder and does not necessarily mean a complete reduction in the severity of one or more symptoms associated with a disorder. [040] The term “patient” is generally synonymous with the term “subject” and includes all mammals including humans. Examples of patients include humans, livestock such as cows, goats, sheep, pigs, and rabbits, and companion animals such as dogs, cats, rabbits, and horses. Preferably, the patient is a human. [041] Those skilled in the art will appreciate that the invention(s) described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention(s) includes all such variations and modifications. The invention(s) also includes all the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations or any two or more of steps or features unless specifically stated otherwise. [042] The present invention(s) is not to be limited in scope by the specific embodiments described herein, which are intended for the purpose of exemplification only. Functionally Attorney Docket No. MDA0075-401-PC // MDA22-068 equivalent products, compositions, and methods are clearly within the scope of the invention(s), as described herein. [043] It is appreciated that certain features of the invention(s), which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the invention(s), which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination. [044] The compounds disclosed herein can exist as pharmaceutically acceptable salts. The present disclosure includes compounds listed herein in the form of salts, including acid addition salts. Suitable salts include those formed with both organic and inorganic acids. Such acid addition salts will normally be pharmaceutically acceptable. However, salts of non- pharmaceutically acceptable salts may be of utility in the preparation and purification of the compound in question. Basic addition salts may also be formed and be pharmaceutically acceptable. For a more complete discussion of the preparation and selection of salts, refer to Pharmaceutical Salts: Properties, Selection, and Use (Stahl, P. Heinrich. Wiley-VCHA, Zurich, Switzerland, 2002). [045] The term “pharmaceutically acceptable salt,” as used herein, represents salts or zwitterionic forms of the compounds disclosed herein which are water or oil-soluble or dispersible and therapeutically acceptable as defined herein. The salts can be prepared during the final isolation and purification of the compounds or separately by reacting the appropriate compound in the form of the free base with a suitable acid. Representative acid addition salts include acetate, adipate, alginate, L-ascorbate, aspartate, benzoate, benzenesulfonate (besylate), bisulfate, butyrate, camphorate, camphorsulfonate, citrate, digluconate, formate, fumarate, gentisate, glutarate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate (isethionate), lactate, maleate, malonate, DL-mandelate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylproprionate, phosphonate, picrate, pivalate, propionate, pyroglutamate, succinate, sulfonate, tartrate, L-tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, para-toluenesulfonate (p-tosylate), and undecanoate. Also, basic groups in the compounds disclosed herein can be quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl, diethyl, dibutyl, and diamyl sulfates; decyl, lauryl, myristyl, and steryl chlorides, bromides, and iodides; and benzyl and phenethyl bromides. Examples of acids which can be employed to form Attorney Docket No. MDA0075-401-PC // MDA22-068 pharmaceutically acceptable addition salts include inorganic acids such as hydrochloric, hydrobromic, sulfuric, and phosphoric, and organic acids such as oxalic, maleic, succinic, and citric. Salts can also be formed by coordination of the compounds with an alkali metal or alkaline earth ion. Hence, the present disclosure contemplates sodium, potassium, magnesium, and calcium salts of the compounds disclosed herein, and the like. [046] Basic addition salts can be prepared during the final isolation and purification of the compounds by reacting a carboxy group with a suitable base such as the hydroxide, carbonate, or bicarbonate of a metal cation or with ammonia or an organic primary, secondary, or tertiary amine. The cations of pharmaceutically acceptable salts include lithium, sodium, potassium, calcium, magnesium, and aluminum, as well as nontoxic quaternary amine cations such as ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, dicyclohexylamine, procaine, dibenzylamine, N,N-dibenzylphenethylamine, 1-ephenamine, and N,N'-dibenzylethylenediamine. Other representative organic amines useful for the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, and piperazine. [047] Provided herein is a compound of structural Formula I: or a salt thereof, wherein: X is chosen from N and CR ¹⁰ ; W, Y, and Z are independently chosen from N and C; R ¹ is chosen from OH and NH2; each occurrence of R ³ is chosen from hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, carbonyl, cyano, halogen, hydroxyl, amino, sulfonyl, sulfonylamino, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, wherein aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is optionally substituted with one or two groups independently chosen from C1-C3 alkyl, C1-C3 alkoxy, cyano, halogen, hydroxyl, and amino; Attorney Docket No. MDA0075-401-PC // MDA22-068 R ⁴ is chosen from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each of which is optionally substituted with one, two, or three groups independently chosen from C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 cycloalkoxy, C1-C6 halocycloalkoxy, carbonyl, C ₁ -C ₆ alkyl sulfonyl, halogen, and cyano; R ⁵ and R ⁶ are independently chosen from hydrogen and C1-C3 alkyl; R ⁷ and R ⁸ are independently chosen from hydrogen and C ₁ -C ₃ alkyl; k is 1, 2, or 3; R ¹⁰ is hydrogen; and n is 0 or 1. [048] Also provided herein is a compound of structural Formula I: or a salt thereof, wherein: R ¹ is chosen from OH and NH2; each occurrence of R ³ is chosen from hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, carbonyl, cyano, halogen, hydroxyl, amino, sulfonyl, sulfonylamino, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, wherein aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is optionally substituted with one or two groups independently chosen from C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, cyano, halogen, hydroxyl, and amino; R ⁴ is chosen from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each of which is optionally substituted with one, two, or three groups independently chosen from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 cycloalkoxy, C ₁ -C ₆ halocycloalkoxy, carbonyl, C ₁ -C ₆ alkyl sulfonyl, halogen, and cyano; R ⁵ and R ⁶ are independently chosen from hydrogen and C ₁ -C ₃ alkyl; R ⁷ and R ⁸ are independently chosen from hydrogen and C1-C3 alkyl; k is 1, 2, or 3; and n is 0 or 1. [049] In some embodiments, k is 1. [050] In some embodiments, k is 2. Attorney Docket No. MDA0075-401-PC // MDA22-068 [051] In some embodiments, k is 3. [052] In some embodiments, W is N. [053] In some embodiments, X is N. [054] In some embodiments, Y is C. [055] In some embodiments, Z is C. [056] In some embodiments, W is N, X is N, Y is C, and Z is C. [057] In some embodiments, the compound of structural Formula I is a compound of structural Formula II or a salt thereof. [058] In some embodiments, R ⁴ is phenyl optionally substituted with one, two, or three groups independently chosen from halogen, C1-C3 alkyl, and C1-C3 alkoxy. [059] In some embodiments, R ⁴ is phenyl optionally substituted with one, two, or three groups independently chosen from halogen, C1-C3 haloalkyl, C1-C3 haloalkoxy, C1-C3 alkyl, and C1-C3 alkoxy. [060] In some embodiments, R ⁴ is phenyl optionally substituted with one, two, or three groups independently chosen from fluoro, chloro, and methoxy. [061] In some embodiments, R ⁴ is phenyl optionally substituted with one, two, or three groups independently chosen from fluoro, chloro, trifluoromethyl, trifluoromethoxy, difluoromethyl, difluoromethoxy, isopropoxy, ethoxy, and methoxy. [062] In some embodiments, R ⁴ is 3,4-difluorophenyl, 3-fluoro-4-methoxyphenyl, 2,4,5- trifluorophenyl, and 2,5-difluoro-4-methoxyphenyl. [063] In some embodiments, R ⁴ is 3,4-difluorophenyl, 3-fluoro-4-methoxyphenyl, 2,4,5- trifluorophenyl, 3-fluoro-4-trifluoromethoxyphenyl, 4-difluoromethoxy-3-fluorophenyl, 4- ethoxy-3-fluorophenyl, 3-fluoro-4-trifluoromethylphenyl, 3-fluoro-4-isopropoxyphenyl, 4- difluoromethyl-3-fluorophenyl, and 2,5-difluoro-4-methoxyphenyl. [064] In some embodiments, the compound of structural Formula I is a compound of structural Formula III Attorney Docket No. MDA0075-401-PC // MDA22-068 or a salt thereof, p is 0, 1, 2, or 3; and each occurrence of R ¹¹ is independently chosen from halogen and C1-C3 alkoxy. [065] In some embodiments, the compound of structural Formula I is a compound of structural Formula III or a salt thereof, p is 0, 1, 2, or 3; and each occurrence of R ¹¹ is independently chosen from halogen, C1-C3 haloalkyl, C1-C3 haloalkoxy, and C ₁ -C ₃ alkoxy. [066] In some embodiments, the compound of structural Formula I is a compound of structural Formula IV or a salt thereof, p is 0, 1, 2, or 3; and each occurrence of R ¹¹ is independently chosen from halogen and C1-C3 alkoxy. Attorney Docket No. MDA0075-401-PC // MDA22-068 [067] In some embodiments, R ¹⁰ is chloro. [068] In some embodiments, R ¹⁰ is H. [069] In some embodiments, the compound of structural Formula I is a compound of structural Formula V or a salt thereof, p is 0, 1, 2; 3 and each occurrence of R ¹¹ is independently chosen from halogen and C ₁ -C ₃ alkoxy. [070] In some embodiments, the compound of structural Formula I is a compound of structural Formula VI or a salt thereof, p is 0, 1, 2, or 3; and each occurrence of R ¹¹ is independently chosen from halogen and C ₁ -C ₃ alkoxy. [071] In some embodiments, the compound of structural Formula I is a compound of structural Formula VII

Attorney Docket No. MDA0075-401-PC // MDA22-068 or a salt thereof, wherein p is 0, 1, 2, or 3; and each occurrence of R ¹¹ is independently chosen from halogen and C1-C3 alkoxy. [072] In some embodiments, the compound of structural Formula I is a compound of structural Formula VII or a salt thereof, p is 0, 1, 2, or 3; and each occurrence of R ¹¹ is independently chosen from halogen, C1-C3 haloalkyl, C1-C3 haloalkoxy, and C1-C3 alkoxy. [073] In some embodiments, p is 0. [074] In some embodiments, p is 1. [075] In some embodiments, p is 1 and R ¹¹ is fluoro. [076] In some embodiments, p is 2. [077] In some embodiments, p is 2 and each occurrence of R ¹¹ is fluoro. [078] In some embodiments, p is 2 and one occurrence of R ¹¹ is fluoro and the other occurrence of R ¹¹ is C ₁ -C ₃ alkoxy. [079] In some embodiments, p is 2 and each occurrence of R ¹¹ is independently chosen from fluoro, trifluoromethoxy, difluoromethoxy, ethoxy, isopropoxy, trifluoromethyl, and difluoromethyl. [080] In some embodiments, p is 3. [081] In some embodiments, p is 3 and each occurrence of R ¹¹ is fluoro. [082] In some embodiments, p is 3 and at least one occurrence of R ¹¹ is C1-C3 alkoxy. [083] In some embodiments, p is 3, one occurrence of R ¹¹ is C1-C3 alkoxy, and the other occurrences of R ¹¹ are fluoro. [084] In some embodiments, each occurrence of R ¹¹ is independently chosen from fluoro, trifluoromethoxy, difluoromethoxy, methoxy, ethoxy, isopropoxy, trifluoromethyl, and difluoromethyl. Attorney Docket No. MDA0075-401-PC // MDA22-068 [085] In some embodiments, R ³ is C(O)NHR ⁷ wherein R ⁷ is C ₁ -C ₃ alkyl. [086] In some embodiments, R ⁷ is methyl. [087] In some embodiments, R ³ is monocyclic heteroaryl optionally substituted with one or two groups independently chosen from C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, cyano, and halogen. [088] In some embodiments, R ³ is pyridinyl optionally substituted with one or two groups independently chosen from C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, cyano, and halogen. [089] In some embodiments, R ³ is 2-pyridinyl optionally substituted with one or two groups independently chosen from fluoro, chloro, and methoxy. [090] In some embodiments, R ³ is 2-pyridinyl. [091] In some embodiments, n is 0. [092] In some embodiments, n is 1. [093] In some embodiments, the structure is chosen from: , , , Attorney Docket No. MDA0075-401-PC // MDA22-068 , , [094] salts possible to present them as a pharmaceutical formulation. [095] Also provided is a pharmaceutical formulation comprising a compound as disclosed herein, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier. [096] In some embodiments, the pharmaceutical formulation is formulated for oral administration. [097] In some embodiments, the oral pharmaceutical formulation is chosen from a tablet and a capsule. Attorney Docket No. MDA0075-401-PC // MDA22-068 [098] The formulations include those suitable for oral, parenteral (including subcutaneous, intradermal, intramuscular, intravenous, intraarticular, and intramedullary), intraperitoneal, transmucosal, transdermal, rectal and topical (including dermal, buccal, sublingual and intraocular) administration although the most suitable route may depend upon for example the condition and disorder of the recipient. The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Typically, these methods include the step of bringing into association a compound, or pharmaceutically acceptable salts thereof, of the subject disclosure or a pharmaceutically acceptable salt thereof ("active ingredient") with the carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation. [099] Formulations of the compounds, or pharmaceutically acceptable salts thereof disclosed herein suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The active ingredient may also be presented as a bolus, electuary or paste. [0100] Pharmaceutical formulations which can be used orally include tablets, push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. Tablets may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with binders, inert diluents, or lubricating, surface active or dispersing agents. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound, or a pharmaceutically acceptable salt thereof, moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein. All formulations for oral administration should be in dosages suitable for such administration. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and / or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds, or pharmaceutically acceptable salts thereof, may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, Attorney Docket No. MDA0075-401-PC // MDA22-068 or liquid polyethylene glycols. In addition, stabilizers may be added. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, Carbopol® gel, polyethylene glycol, and / or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses, or pharmaceutically acceptable salts thereof. [0101] The compounds, or a pharmaceutically acceptable salt thereof, may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The formulations may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. The formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in powder form or in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example, saline or sterile pyrogen-free water, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described. [0102] Formulations for parenteral administration include aqueous and non-aqueous (oily) sterile injection solutions of the active compounds, or a pharmaceutically acceptable salt thereof, which may contain antioxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non- aqueous sterile suspensions which may include suspending agents and thickening agents. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds, or pharmaceutically acceptable salts thereof, to allow for the preparation of highly concentrated solutions. [0103] In addition to the formulations described previously, the compounds, or pharmaceutically acceptable salts thereof, may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the Attorney Docket No. MDA0075-401-PC // MDA22-068 compounds, or pharmaceutically acceptable salts thereof, may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. [0104] For buccal or sublingual administration, the formulations may take the form of tablets, lozenges, pastilles, or gels formulated in conventional manner. Such formulations may comprise the active ingredient in a flavored basis such as sucrose and acacia or tragacanth. [0105] The compounds, or pharmaceutically acceptable salts thereof, may also be formulated in rectal formulations such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter, polyethylene glycol, or other glycerides. [0106] Certain compounds, or pharmaceutically acceptable salts thereof, disclosed herein may be administered topically, that is by non-systemic administration. This includes the application of a compound, or a pharmaceutically acceptable salt thereof, disclosed herein externally to the epidermis or the buccal cavity and the instillation of such a compound, or a pharmaceutically acceptable salt thereof, into the ear, eye and nose, such that the compound (or pharmaceutically acceptable salt thereof) does not significantly enter the blood stream. In contrast, systemic administration refers to oral, intravenous, intraperitoneal and intramuscular administration. [0107] Formulations suitable for topical administration include liquid or semi-liquid preparations suitable for penetration through the skin to the site of inflammation such as gels, liniments, lotions, creams, ointments or pastes, and drops suitable for administration to the eye, ear or nose. The active ingredient for topical administration may comprise, for example, from 0.001% to 10% w / w (by weight) of the formulation. In some embodiments, the active ingredient may comprise as much as 10% w / w. In some embodiments, it may comprise less than 5% w / w. In some embodiments, the active ingredient may comprise from 2% w / w to 5% w / w. In some embodiments, it may comprise from 0.1% to 1% w / w of the formulation. [0108] For administration by inhalation, compounds, or pharmaceutically acceptable salts thereof, may be conveniently delivered from an insufflator, nebulizer pressurized packs or other convenient means of delivering an aerosol spray. Pressurized packs may comprise a suitable propellant such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. Alternatively, for administration by inhalation or insufflation, the compounds, and pharmaceutically acceptable salts thereof, according to the disclosure may take the form of a Attorney Docket No. MDA0075-401-PC // MDA22-068 dry powder formulation, for example a powder mix of the compound, or pharmaceutically acceptable salt thereof, and a suitable powder base such as lactose or starch. The powder formulation may be presented in unit dosage form, in for example, capsules, cartridges, gelatin or blister packs from which the powder may be administered with the aid of an inhalator or insufflator. [0109] Preferred unit dosage formulations are those containing an effective dose, or an appropriate fraction thereof, of the active ingredient. [0110] It should be understood that in addition to the ingredients particularly mentioned herein, the formulations described herein may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents. [0111] Also provided herein is a method for treating a disease or condition that benefits from or is treatable by inhibition of nuclear SET domain-containing protein 1 or 2 (NSD1 or NSD2), comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound recited herein, or a salt thereof. [0112] In some embodiments, said disease or condition that benefits from or is treatable by inhibition of NSD 1 or NSD2 is selected from solid tumors, leukemia, myeloma, lymphoma and hypertension. In some embodiments, said disease or condition that benefits from or is treatable by inhibition of NSD1 or NSD2 is breast cancer, cervical cancer, skin cancer (particularly skin squamous cell carcinoma) , ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, lung cancer, hepatocellular carcinoma, head and neck cancer, peripheral nerve sheath tumor, osteosarcoma, multiple myeloma, neuroblastoma, leukemia (particularly acute lymphoblastic leukemia), non-Hodgkin’s lymphoma (particularly mantle cell lymphoma), and pulmonary arterial hypertension. [0113] In some embodiments, said disease or condition is chosen from solid tumors, leukemia, myeloma, lymphoma and hypertension. [0114] In some embodiments, said disease or condition is chosen from breast cancer, cervical cancer, skin cancer , ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, lung cancer, hepatocellular carcinoma, head and neck cancer, peripheral nerve sheath tumor, osteosarcoma, multiple myeloma, neuroblastoma, leukemia, non-Hodgkin’s lymphoma, and pulmonary arterial hypertension. [0115] In some embodiments, the leukemia is acute lymphoblastic leukemia. [0116] In some embodiments, the lymphoma is mantle cell lymphoma. [0117] In some embodiments, the skin cancer is skin squamous cell carcinoma. Attorney Docket No. MDA0075-401-PC // MDA22-068 [0118] Also provided are methods of inhibiting at least one NSD function comprising the step of contacting NSD with a compound as described herein, or a pharmaceutically acceptable salt thereof. The cell phenotype, cell proliferation, activity of NSD, change in biochemical output produced by active NSD, expression of NSD, or binding of NSD with a natural binding partner may be monitored. Such methods may be modes of treatment of disease, biological assays, cellular assays, biochemical assays, or the like. [0119] Also provided herein are methods of treatment of an NSD-mediated disease comprising the administration of a therapeutically effective amount of a compound as disclosed herein, or a pharmaceutically acceptable salt thereof, to a patient in need thereof. [0120] Also provided herein are methods of treatment of an inflammatory component of an NSD-mediated disease. [0121] Also provided herein is a method of inhibition of NSD comprising contacting NSD with a compound as disclosed herein, or a pharmaceutically acceptable salt thereof. [0122] Also provided is a method of modulation of an NSD-mediated function in a subject comprising the administration of a therapeutically effective amount of a compound as disclosed herein, or a pharmaceutically acceptable salt thereof. [0123] In some embodiments, the compounds, pharmaceutically acceptable salts formulations, and methods disclosed herein may be co-administered with another therapeutic agent. [0124] Compounds, or pharmaceutically acceptable salts thereof, may be administered orally or via injection at a dose of from 0.1 to 500 mg / kg per day. The dose range for adult humans is generally from 5 mg to 2 g / day. Tablets or other forms of presentation provided in discrete units may conveniently contain an amount of one or more compounds, or pharmaceutically acceptable salts thereof, which is effective at such dosage or as a multiple of the same, for instance, units containing 5 mg to 500 mg, usually around 10 mg to 200 mg. [0125] The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. [0126] The compounds, or pharmaceutically acceptable salts thereof, can be administered in various modes, e.g., orally, topically, or by injection. The precise amount of compound, or pharmaceutically acceptable salt thereof, administered to a patient will be the responsibility of the attendant physician. The specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed, or pharmaceutically acceptable salt thereof, the age, body weight, general health, sex, diets, time Attorney Docket No. MDA0075-401-PC // MDA22-068 of administration, route of administration, rate of excretion, drug combination, the precise disorder being treated, and the severity of the indication or condition being treated. Also, the route of administration may vary depending on the condition and its severity. [0127] In certain instances, it may be appropriate to administer at least one of the compounds described herein (or a pharmaceutically acceptable salt thereof) in combination with another therapeutic agent. By way of example only, if one of the side effects experienced by a patient upon receiving one of the compounds herein, or pharmaceutically acceptable salt thereof, is hypertension, then it may be appropriate to administer an anti- hypertensive agent in combination with the initial therapeutic agent. Or, by way of example only, the therapeutic effectiveness of one of the compounds described herein, or pharmaceutically acceptable salts thereof, may be enhanced by administration of an adjuvant (i.e., by itself the adjuvant may only have minimal therapeutic benefit, but in combination with another therapeutic agent, the overall therapeutic benefit to the patient is enhanced). Or, by way of example only, the benefit of experienced by a patient may be increased by administering one of the compounds described herein, or pharmaceutically acceptable salts thereof, with another therapeutic agent (which also includes a therapeutic regimen) that also has therapeutic benefit. By way of example only, in a treatment for diabetes involving administration of one of the compounds described herein, or pharmaceutically acceptable salts thereof, increased therapeutic benefit may result by also providing the patient with another therapeutic agent for diabetes. In any case, regardless of the disease, disorder or condition being treated, the overall benefit experienced by the patient may simply be additive of the two therapeutic agents or the patient may experience a synergistic benefit. [0128] In any case, the multiple therapeutic agents (at least one of which is a compound disclosed herein, or a pharmaceutically acceptable salt thereof) may be administered in any order or even simultaneously. If simultaneously, the multiple therapeutic agents may be provided in a single, unified form, or in multiple forms (by way of example only, either as a single pill or as two separate pills). One of the therapeutic agents may be given in multiple doses, or both may be given as multiple doses. If not simultaneous, the timing between the multiple doses may be any duration of time ranging from a few minutes to four weeks. [0129] Further embodiments include the embodiments disclosed in the following Examples, which is not to be construed as limiting in any way. SCHEMES Attorney Docket No. MDA0075-401-PC // MDA22-068 Scheme I [0130] Referring to Scheme I, Step 1, to a solution of the compound of Formula 101 (R = alkyl) in a polar aprotic solvent, such as DMSO, is added a non-nucleophilic base, such as DIPEA and a compound of Formula 102. The mixture is stirred at elevated temperature for 24–72 h. During this time, the progress of the reaction can be followed by chromatography, for example, TLC. The product, a compound of Formula 103, is isolated and purified using methods known in the art. [0131] Referring to Scheme I, Step 2, to a solution of the compound of Formula 103 in an organic solvent, such as DCM, is added a brominating agent, such as NBS. The mixture is stirred at room temperature for 0.5-1 h. During this time, the progress of the reaction can be followed by chromatography, for example, TLC. The product, a compound of Formula 104, is isolated using methods known in the art. [0132] Referring to Scheme I, Step 3, to a solution of the compound of Formula 104 in a polar aprotic solvent, such as dioxane, is added a compound of Formula 105 (R = alkyl, such as methyl, or hydrogen, or in combination with a second R group forms a heterocycloalkyl, such as pinacol borane), a base, such as potassium carbonate, and a catalyst, such as Pd(dppf)Cl ₂ . The mixture is degassed and stirred at elevated temperature for 2–4 h. During Attorney Docket No. MDA0075-401-PC // MDA22-068 this time, the progress of the reaction can be followed by chromatography, for example, TLC. The product, a compound of Formula 106, is isolated and purified using methods known in the art. [0133] Referring to Scheme I, Step 4, to a solution of the compound of Formula 106 in a polar aprotic solvent, such as THF, is added a reducing agent, such as lithium aluminum hydride. The mixture is stirred at room temperature for 0.1–3 h. During this time, the progress of the reaction can be followed by chromatography, for example, TLC. The product, a compound of Formula 107, is isolated and purified using methods known in the art. [0134] Referring to Scheme I, Step 5, to a solution of the compound of Formula 108 (PG = protecting group; Q = hydrogen) in a polar aprotic solvent, such as tetrahydrofuran, at reduced temperature, such as 0°C, is added a compound of Formula 107, tributylphosphine, and an azodicarboxylate. The resulting mixture is stirred at room temperature for between 1– 3 h. During this time, the progress of the reaction can be followed by chromatography, for example, TLC. The product, a compound of Formula 109, is isolated and purified using methods known in the art. [0135] Referring to Scheme I, Step 6, to a solution of the compound of Formula 109 in a polar solvent, such as dichloromethane, is added a strong acid, such as trifluoroacetic acid. The mixture is stirred at room temperature for between 1–3 h. During this time, the progress of the reaction can be followed by chromatography, for example, TLC. The product, a compound of Formula I, is isolated and purified using methods known in the art. Individual enantiomers can be separated by using methods known in the art, such as chiral chromatography. EXAMPLES Example 1 3-amino-1-(4-((6-amino-9H- 4-methoxyphenyl)thiazol-5- yl)- Attorney Docket No. MDA0075-401-PC // MDA22-068 [0136] benzyl 2,4-dioxo-1,3,7-triazaspiro[4.5]decane-7-carboxylate To a suspension of benzyl 3-oxopiperidine-1-carboxylate (10.0 g, 42.9 mmol) in MeOH (30.0 mL) and H ₂ O (70.0 mL) was added (NH ₄ ) ₂ CO ₃ (10.0 g, 42.9 mmol) and TMSCN (10.0 g, 42.9 mmol). The reaction mixture was stirred at 40 ^o C for 48 hours and then the resulting solid was filtered and washed with water 500 (mL) to afford benzyl 2,4-dioxo-1,3,7- triazaspiro[4.5]decane-7-carboxylate (11.0 g, 84.6%) as a yellow solid. MS (ES ⁺ ) C15H17N3O4, requires:303, found: 304 [M+H] ⁺ . [0137] 7-benzyl [4.5]decane-1,3,7- tricarboxylate To a suspension of benzyl 2,4-dioxo-1,3,7-triazaspiro[4.5]decane-7- carboxylate (7000 mg, 23.1 mmol) in DME (100 mL) was added di-tert-butyl dicarbonate (18480 mg, 92.4 mmol) TEA (2333 mg, 23.1 mmol) and DMAP (30 mg). The mixture was stirred at 25 ^o C for 18 hours. The resulting solid was filtered and washed with water 500 (mL) to afford 7-benzyl 1,3-di-tert-butyl 2,4-dioxo-1,3,7-triazaspiro[4.5]decane-1,3,7- tricarboxylate (5000 mg, 43.0%) as a yellow solid. MS (ES ⁺ ) C25H33N3O8, Srequires:503, found: 504 [M+H] ⁺ . [0138] 3-amino- acid To a suspension of 7- [4.5]decane-1,3,7- tricarboxylate (5000 mg, 9.94 mmol) in THF(50 mL) was added 1.0M LiOH aqueous solution (60 mL) and the resulting mixture was stirred at 25 ^o C for 18 hours. Then solvent was removed under reduced pressure. 1.0M HCl (60 mL) was added at 0 ^o C to adjust the PH = 6~7. The resulting solid was filtered and washed with water 500 (mL) to afford 3-amino-1- Attorney Docket No. MDA0075-401-PC // MDA22-068 ((benzyloxy)carbonyl)piperidine-3-carboxylic acid (2600 mg, 94.1%) as an off white solid. MS (ES ⁺ ) C14H18N2O4 requires:278, found: 279 [M+H] ⁺ . [0139] 1-((benzyloxy)carbonyl)-3-((tert-butoxycarbonyl)amino)piperi dine-3- carboxylic acid To a suspension of 3-amino-1-((benzyloxy)carbonyl)piperidine-3- carboxylic acid (2600 mg, 9.35 mmol) in THF (30 mL) and H ₂ O (30 mL) was added (Boc) ₂ O (3057 mg, 14.02 mmol) and Na2CO3(1486 mg, 14.02 mmol) and the resulting mixture was stirred at 25 ^o C for 18 hours. Solvent was removed under reduced pressure.1.0M HCl (60 mL) was added at 0 ^o C to adjust the PH = 6~7. The resulting solid was filtered and washed with water 500 (mL) to afford 1-((benzyloxy)carbonyl)-3-((tert- butoxycarbonyl)amino)piperidine-3-carboxylic acid (2200 mg, 62.2%).as a yellow solid. MS (ES ⁺ ) C19H26N2O6, requires:378, found: 379 [M+H] ⁺ . [0140] benzyl 3-((tert- piperidine-1- carboxylate To a suspension of 1-((benzyloxy)carbonyl)-3-((tert- butoxycarbonyl)amino)piperidine-3-carboxylic acid (2200 mg, 5.82 mmol) in DMF (25 mL) at 25 ^o C was added methanamine hydrochloride (779.9 mg, 11.64 mmol), TEA (1175.6 mg, 11.64 mmol) and HATU (4423.2 mg, 11.64 mmol). The resulting mixture was stirred at 25 ^o C overnight. The mixture was poured into water (100 mL) and extracted with EtOAc (100 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated to afford benzyl 3-((tert-butoxycarbonyl)amino)-3-(methylcarbamoyl)piperidine -1-carboxylate (2000 mg, 87.7%) as a yellow solid. MS (ES ⁺ ) C20H29N3O5, requires:391, found: 392 [M+H] ⁺ . Attorney Docket No. MDA0075-401-PC // MDA22-068 [0141] tert-butyl (3-(methylcarbamoyl)piperidin-3-yl)carbamate To a degassed suspension of benzyl 3-((tert-butoxycarbonyl)amino)-3-(methylcarbamoyl)piperidine -1- carboxylate (2000 mg, 5.11 mmol) in MeOH (20.0 mL) was added Pd/C (500 mg). The resulting mixture was stirred at 25 ^o C under H2 (1 atm) for 2h. The mixture was filtered and concentrated to afford tert-butyl (3-(methylcarbamoyl)piperidin-3-yl)carbamate (1200 mg, 91.4%) as a yellow solid. MS (ES ⁺ ) C12H23N3O3, requires:257, found: 258 [M+H] ⁺ . [0142] piperidin-1- yl)thiazole-4-carboxylate To a solution of ethyl 5-bromothiazole-4-carboxylate (200 mg, 0.855 mmol) and tert-butyl (3-(methylcarbamoyl)piperidin-3-yl)carbamate (219.6 mg, 0.855 mmol) in DMSO (5.0 mL) was added DIPEA (220.6 mg, 1.71 mmol). The mixture was stirred at 120°C for 48 hours. The mixture was poured into water (100 mL) and extracted with EtOAc (100 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated. The residual was purified by silica gel chromatography (EtOAc/PE = 50–60%) to give ethyl 5-(3-((tert-butoxycarbonyl)amino)-3-(methylcarbamoyl)piperid in-1-yl)thiazole- 4-carboxylate (213 mg, 51.7%) as a yellow solid. MS (ES ⁺ ) C18H28N4O5S, requires: 412, found: 413 [M+H] ⁺ . [0143] (methylcarbamoyl)piperidin-1-yl)thiazole-4-carboxylate To a solution of ethyl 5-(3-((tert- butoxycarbonyl)amino)-3-(methylcarbamoyl)piperidin-1-yl)thia zole-4-carboxylate (213 mg, 0.517 mmol) in DCM (10 mL) was added NBS (92.0 mg, 0.517 mmol). The resulting mixture was stirred at 25°C for 0.5 hours then concentrated to give crude ethyl 2-bromo-5-(3-((tert- butoxycarbonyl)amino)-3-(methylcarbamoyl)piperidin-1-yl)thia zole-4-carboxylate Attorney Docket No. MDA0075-401-PC // MDA22-068 compound (220 mg), which could be carried to the next step without further purification. MS (ES ⁺ ) C18H27BrN4O5S, requires: 490, found: 491 [M+H] ⁺ . [0144] ethyl 5-(3-((tert-butoxycarbonyl)amino)-3-(methylcarbamoyl)piperid in-1-yl)- 2-(3-fluoro-4-methoxyphenyl)thiazole-4-carboxylate A degassed suspension of ethyl 2- bromo-5-(3-((tert-butoxycarbonyl)amino)-3-(methylcarbamoyl)p iperidin-1-yl)thiazole-4- carboxylate (220 mg, 0.449 mmol), (3-fluoro-4-methoxyphenyl)boronic acid (76.33 mg, 0.449 mmol), K ₂ CO ₃ (123.9 mg, 0.898 mmol), and Pd(dppf)Cl ₂ (41.2 mg, 0.045 mmol) in dioxane (6 mL) and H2O (2 mL) was stirred at 90°C for 2 hours. The mixture was poured into H ₂ O (100 mL) and extracted with EtOAc (100 mL × 3). The combined organic layers were dried over Na2SO4, filtered and concentrated, and purified by silica gel chromatography (MeOH : DCM = 0–10%) to give ethyl 5-(3-((tert-butoxycarbonyl)amino)-3- (methylcarbamoyl)piperidin-1-yl)-2-(3-fluoro-4-methoxyphenyl )thiazole-4-carboxylate (165 mg, 68.6%) as a yellow solid. MS (ES ⁺ ) C25H33FN4O6S, requires: 536, found: 537 [M+H] ⁺ . [0145] thiazol-5-yl)- 3-(methylcarbamoyl)piperidin-3-yl)carbamate To a solution of ethyl 5-(3-((tert- butoxycarbonyl)amino)-3-(methylcarbamoyl)piperidin-1-yl)-2-( 3-fluoro-4- methoxyphenyl)thiazole-4-carboxylate (165 mg, 0.308 mmol) in THF (5 mL) was added LAH (11.7 mg, 0.308 mmol). The mixture was stirred at 25°C for 1 hour. The mixture was Attorney Docket No. MDA0075-401-PC // MDA22-068 poured into water (100 mL) and extracted with EtOAc (100 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered, concentrated, and purified by silica gel chromatography (10%~50% EtOAc in Petroleum ether) to give tert-butyl (1-(2-(3-fluoro-4- methoxyphenyl)-4-(hydroxymethyl)thiazol-5-yl)-3-(methylcarba moyl)piperidin-3- yl)carbamate (106 mg, 69.7 %) as a yellow solid. MS (ES ⁺ ) C23H31FN4O5S, requires: 494, found: 495 [M+H] ⁺ . [0146] tert-butyl -3- (methylcarbamoyl)piperidin-1-yl)-2-(3-fluoro-4-methoxyphenyl )thiazol-4-yl)methyl)- 9H-purin-6-yl)carbamate To a solution of tert-butyl (1-(2-(3-fluoro-4-methoxyphenyl)-4- (hydroxymethyl)thiazol-5-yl)-3-(methylcarbamoyl)piperidin-3- yl)carbamate (106 mg, 0.215 mmol) and tert-butyl (tert-butoxycarbonyl)(9H-purin-6-yl)carbamate (72.0 mg, 0.215 mmol) in THF (2 mL) at 0°C was added DIAD (65.9 mg, 0.430 mmol) and PBu3 (65.9 mg, 0.430 mmol). The resulting mixture was stirred at room temperature for 2 hours. The mixture was poured into water (5 mL) and extracted with EtOAc (30 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered, and concentrated to give tert-butyl (tert- butoxycarbonyl)(9-((5-(3-((tert-butoxycarbonyl)amino)-3-(met hylcarbamoyl)piperidin-1-yl)- 2-(3-fluoro-4-methoxyphenyl)thiazol-4-yl)methyl)-9H-purin-6- yl)carbamate (102 mg, 58.5%) as a yellow solid. MS (ES ⁺ ) C38H50FN9O8S, requires: 811, found: 812 [M+H] ⁺ .

Attorney Docket No. MDA0075-401-PC // MDA22-068 [0147] 3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-2-(3-fluoro-4- methoxyphenyl)thiazol-5-yl)-N-methylpiperidine-3-carboxamide To a solution of tert- butyl (tert-butoxycarbonyl)(9-((5-(3-((tert-butoxycarbonyl)amino)- 3- (methylcarbamoyl)piperidin-1-yl)-2-(3-fluoro-4-methoxyphenyl )thiazol-4-yl)methyl)-9H- purin-6-yl)carbamate (102 mg, 0.126 mmol) in DCM (10 mL) was added TFA (2 mL). The resulting mixture was stirred at room temperature for 2 hours. The mixture was poured into aq. NaHCO3 (100 mL) and extracted with EtOAc (100 mL × 3). The combined organic phases were dried over Na ₂ SO ₄ , filtered, and concentrated and purified by silica gel chromatography (MeOH : DCM = 0–10%) to give 3-amino-1-(4-((6-amino-9H-purin-9- yl)methyl)-2-(3-fluoro-4-methoxyphenyl)thiazol-5-yl)-N-methy lpiperidine-3-carboxamide (51.0 mg, 79%) as a white solid. MS (ES ⁺ ) C23H26FN9O2S, requires: 511, found: 512 [M+H] ⁺ . ¹ H NMR (400 MHz, MeOD) δ 8.50 (s, 1H), 8.38 (s, 1H), 7.65-7.60 (m, 2H), 7.15 (t, Hz, 2H), 3.91 (s, 3H), 3.24-3.17 (m, 2H), 2.93-2.87 (m, 1H), 2.80 (s, 3H), 2.18-2.10 (m, 3H), 2.04-1.96 (m, 2H). [0148] The following Examples were synthesized with procedures that were similar to the examples disclosed herein and can generally be made by methods disclosed herein. The Examples may be made as free bases or as TFA salts. Table 1. NSD Inhibitors

Attorney Docket No. MDA0075-401-PC // MDA22-068 s . Attorney Docket No. MDA0075-401-PC // MDA22-068 s . Attorney Docket No. MDA0075-401-PC // MDA22-068 s . Attorney Docket No. MDA0075-401-PC // MDA22-068 s . Tab Calc. Mass / Ex. Obsd. Mass ), Attorney Docket No. MDA0075-401-PC // MDA22-068 ), - ). d, , d, = ), = ), = - d, J , - ), Attorney Docket No. MDA0075-401-PC // MDA22-068 m, , , J 2 ), ), 2 ), Attorney Docket No. MDA0075-401-PC // MDA22-068 [0149] The activity of the compounds in Examples 1-16 as NSD inhibitors is illustrated in the following assays. The compounds described herein can be tested for efficacy in the treatment or prevention of symptoms or indications of NSD-mediated diseases using techniques well known to those in the art. Biological Activity Assays [0150] The biochemical activities of NSD1 and 2 were determined by the HotSpot™ Kinase Assay at Reaction Biology® (Malvern, PA, USA). Briefly, 0.05 mg/mL chicken oligonucleosomes was mixed with 10 nM and 2 nM of NSD1 (Reaction Biology® HMT-21- 139) and NSD2 (Reaction Biology® HMT-21-138), respectively. Upon the treatment of inhibitors at varying concentrations, the reaction mixtures were pre-incubated for 20 min before the addition of 1 µM S-Adenosyl-L-[methyl-3H]methionine. After incubation for 1 h at 30°C, the mixtures were delivered to filter-paper for detection. IC50 values were calculated using GraphPad Prism software. HCC15 Cellular Target Engagement Assay Monitoring H3K36 Dimethylation [0151] Cellular target engagement of NSD1/2/3 was measured via an AlphaLISA (PerkinElmer®, AL723C) readout of H3K36me2 in HCC15 cells. HCC15 cells were cultured in RPMI media (Gibco®, 11875-093) containing 10% FBS (Sigma®, F2442) and 1x PenStrep (Millipore®, TMS-AB2-C). For the Target engagement assay, cells were harvested and resuspended in culture medium. Cells were seeded onto a 384-well white PerkinElmer® Tissue Culture Plate (PerkinElmer®, 6007680) at a density of 1,000 cells/well in a volume of 40 µL. The tissue culture plate was incubated for 24 hours at 37°C with 5% CO ₂ and ambient O2. Stock solutions of the test compounds were prepared in 100% DMSO (Sigma®, D2650) and serially diluted 1:3 using 100% DMSO. Compounds were additionally diluted 1:40 in culture medium, and 10 µL/well were transferred to the tissue culture plate. Following the compound addition, the microplate was incubated at 37°C for 72 hours. After the 72 hour incubation, the cell plate was washed one time in PBS. The AlphaLISA assay was performed according to the PerkinElmer® assay manual. The AlphaLISA signal was quantified using the Envision® Multilabel plate reader. Cell viability was performed on a duplicate plate using CellTiter-Glo 2.0 (Promega® G9243) per manufacturer’s instructions. The luminescence signal was then quantified on the Biotek™ Neo plate reader. KMS-11 Cells Target Engagement Assay Monitoring H3K36 Dimethylation Attorney Docket No. MDA0075-401-PC // MDA22-068 [0152] Cellular target engagement of NSD1/2/3 was measured via an AlphaLISA (PerkinElmer®, AL723C) readout of H3K36me2 in KMS-11 cells. KMS-11 cells were cultured in RPMI media (Gibco®, 11875-093) containing 10% FBS (Sigma®, F2442) and 1x PenStrep (Millipore®, TMS-AB2-C). For the Target engagement assay, cells were harvested and re-suspended in culture medium. Cells were seeded onto a 384-well white PerkinElmer® Tissue Culture Plate (PerkinElmer®, 6007680) at a density of 500 cells/well in a volume of 40 µL. The tissue culture plate was incubated for 24 hours at 37°C with 5% CO2 and ambient O ₂ . Stock solutions of the test compounds were prepared in 100% DMSO (Sigma®, D2650) and serially diluted 1:3 using 100% DMSO. Compounds were additionally diluted 1:40 in culture medium, and 10 µL/well were transferred to the tissue culture plate. Following the compound addition, the microplate was incubated at 37°C for 72 hours. After the 72 hour incubation, the AlphaLISA assay was performed using PerkinElmer® AlphaLISA assay kit. 13 µL of 1x cell histone lysis buffer were added to the plate followed by a 15 minute incubation with shaking.15 µL of the cell histone extraction buffer were added followed by a 10 minute incubation with shaking.2.5 µL of H3K36me2 acceptor beads and biotinylated antibody diluted in 1x cell histone detection buffer were added for final concentrations of 20 µg/ml and 3 nM, respectively, followed by a 1 hr incubation.2.5 µL of streptavidin donor beads diluted in 1x cell histone detection buffer were added for a final concentration of 20 µg/mL followed by an overnight incubation in the dark. The AlphaLISA signal was quantified using the Envision® Multilabel plate reader. Cell viability was performed on a duplicate plate using CellTiter-Glo 2.0 (Promega® G9243) per manufacturer’s instructions. The luminescence signal was then quantified on the Biotek™ Neo plate reader. Table 3. NSD 1/2 and HCC15 Cellular Assay Monitoring H3K36 Dimethylation E _x. ^{Avg NSD1} Avg NSD2 Avg HCC15 Avg KMS11 M Attorney Docket No. MDA0075-401-PC // MDA22-068 1 M [0153] All references, patents or applications, U.S. or foreign, cited in the application are hereby incorporated by reference as if written herein in their entireties. Where any inconsistencies arise, material literally disclosed herein controls. [0154] From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this disclosure, and without departing from the spirit and scope thereof, can make various changes and modifications of the disclosure to adapt it to various usages and conditions.