Title:
NTCP INHIBITOR
Document Type and Number:
WIPO Patent Application WO/2019/139126
Kind Code:
A1
Abstract:
Provided is a sodium taurocholate cotransporting polypeptide (NTCP) inhibitor which comprises a cyclic peptide having an Xw1-W-Xw2-W structure (Xw1 and Xw2 are each independently T, S, I, L, or V, or N-alkyl amino acids thereof) or a P-Xp1-Xp2-H structure (Xp1 is an optional amino acid, and Xp2 is I, L, or V, or N-alkyl amino acids thereof), or a pharmaceutically acceptable salt thereof.
Inventors:
SUGA HIROAKI (JP)
PASSIOURA TOBY (JP)
WAKITA TAKAJI (JP)
WATASHI KOICHI (JP)
PASSIOURA TOBY (JP)
WAKITA TAKAJI (JP)
WATASHI KOICHI (JP)
Application Number:
PCT/JP2019/000699
Publication Date:
July 18, 2019
Filing Date:
January 11, 2019
Export Citation:
Assignee:
UNIV TOKYO (JP)
JAPAN AS REPRESENTED BY THE DIRECTOR GENERAL OF NAT INSTITUTE OF INFECTIOUS DISEASES (JP)
JAPAN AS REPRESENTED BY THE DIRECTOR GENERAL OF NAT INSTITUTE OF INFECTIOUS DISEASES (JP)
International Classes:
A61K38/12; A61P1/16; A61P31/12; A61P31/14; A61P31/20; A61P43/00; C07K5/04; C07K7/06; C07K7/08
Domestic Patent References:
| WO2003092631A2 | 2003-11-13 | |||
| WO2015030014A1 | 2015-03-05 | |||
| WO2008059823A1 | 2008-05-22 |
Foreign References:
| JPS60162000A | 1985-08-23 |
Other References:
SUGA HIROAKI: "Search for cyclic peptides that bind to HBV protein", GRANT-IN-AID FOR SCIENTIFIC RESEARCH ON HEALTH, LABOR AND WELFARE, RESEARCH PROJECT FOR PRACTICAL APPLICATION OF HEPATITIS B DRUG DISCOVERY, STUDY ON ELUCIDATION OF INFECTION REPLICATION MECHANISM OF HEPATITIS B VIRUS, 2012 GENERAL REPORT , 2013, pages 31 - 32, XP009522260
GORDON R DREESMAN, YANUARIO SANCHEZ, IRINA IONESCU-MATIN, JAMES T. SPARROW, HOWARD R. SIX, DARRELL L. PETERSON, F. BLAINE HOLLING: "Antibody to hepatitis B surface antigen after a single inoculation of uncoupled synthetic HBsAg peptide", NATURE, vol. 295, no. 5845, 31 January 1982 (1982-01-31), pages 158 - 160, XP055722227, ISSN: 0028-0836, DOI: 10.1038/295158a0
NKONGOLO, S. ET AL.: "Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-independent interference with the NTCP receptor", JOURNAL OF HEPATOLOGY, vol. 60, 2014, pages 723 - 731, XP028632086, DOI: 10.1016/j.jhep.2013.11.022
NI, Y. ET AL.: "Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes", GASTROENTEROLOGY, vol. 146, 2014, pages 1070 - 1083
YAN H ET AL.: "Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on sodium taurocholate cotransporting polypeptide", J VIROL, vol. 88, 2014, pages 3273 - 3284, XP055598830, DOI: 10.1128/JVI.03478-13
WATASHI K ET AL.: "Interleukin-1 and tumor necrosis factor-alpha trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID", HEPATOLOGY, vol. 59, 2014, pages 1726 - 1737
BLANK A ET AL.: "The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics", CLIN PHARMACOL THER, vol. 00, 2017, pages 1 - 8
MORIMOTO, J.HAYASHI, Y.SUGA, H.: "Discovery of Macrocyclic Peptides Armed with a Mechanism-Based Warhead: Isoform-Selective Inhibition of Human Deacetylase SIRT2", ANGEW. CHEM. INT. ED. ENGL., vol. 51, 2012, pages 3423 - 3427, XP055133046, DOI: 10.1002/anie.201108118
KAWAKAMI, T.MURAKAMI, H.SUGA, H.: "Messenger RNA-programmed incorporation of multiple N-methyl-amino acids into linear and cyclic peptides", CHEM. BIOL., vol. 15, 2008, pages 32 - 42, XP022428215, DOI: 10.1016/j.chembiol.2007.12.008
GOTO, Y.KATOH, T.SUGA, H.: "Flexizymes for genetic code reprogramming", NAT. PROTOC., vol. 6, 2011, pages 779 - 790, XP009158277, DOI: 10.1038/nprot.2011.331
HAYASHI, Y.MORIMOTO, J.SUGA, H.: "In vitro selection of anti-Akt2 thioether-macrocyclic peptides leading to isoform-selective inhibitors", ACS CHEM. BIOL., vol. 7, 2012, pages 607 - 613, XP055133026, DOI: 10.1021/cb200388k
WATASHI, K. ET AL.: "Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP", HEPATOLOGY, vol. 59, 2014, pages 1726 - 1737, XP055474935, DOI: 10.1002/hep.26982
SHIMURA, S. ET AL.: "Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity", JOURNAL OF HEPATOLOGY, vol. 66, 2017, pages 685 - 692, XP029944794, DOI: 10.1016/j.jhep.2016.11.009
IWAMOTO, M. ET AL.: "Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 443, 2014, pages 808 - 813, XP028815147, DOI: 10.1016/j.bbrc.2013.12.052
OGURA, N.WATASHI, K.NOGUCHI, T.WAKITA, T.: "Formation of covalently closed circular DNA in Hep38.7-Tet cells, a tetracycline inducible hepatitis B virus expression cell line", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 452, 2014, pages 315 - 321, XP029067246, DOI: 10.1016/j.bbrc.2014.08.029
ISHIDA, Y. ET AL.: "Novel robust in vitro hepatitis B virus infection model using fresh human hepatocytes isolated from humanized mice", THE AMERICAN JOURNAL OF PATHOLOGY, vol. 185, 2015, pages 1275 - 1285
TSUKUDA, S. ET AL.: "Dysregulation of retinoic acid receptor diminishes hepatocyte permissiveness to hepatitis B virus infection through modulation of sodium taurocholate cotransporting polypeptide (NTCP) expression", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 290, 2015, pages 5673 - 5684, XP055346708, DOI: 10.1074/jbc.M114.602540
WATASHI, K. ET AL.: "Interleukin-1 and tumor necrosis factor-alpha trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 288, 2013, pages 31715 - 31727
KANEKO, M. ET AL.: "A Novel Tricyclic Polyketide, Vanitaracin A, Specifically Inhibits the Entry of Hepatitis B and D Viruses by Targeting Sodium Taurocholate Cotransporting Polypeptide", JOURNAL OF VIROLOGY, vol. 89, 2015, pages 11945 - 11953, XP055481652, DOI: 10.1128/JVI.01855-15
BARTOSCH, B.DUBUISSON, J.COSSET, F.L.: "Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes", THE JOURNAL OF EXPERIMENTAL MEDICINE, vol. 197, 2003, pages 633 - 642, XP002563514, DOI: 10.1084/jem.20021756
NAKAJIMA, S. ET AL.: "Specific inhibition of hepatitis C virus entry into host hepatocytes by fungi-derived sulochrin and its derivatives", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 440, 2013, pages 515 - 520, XP028761550, DOI: 10.1016/j.bbrc.2013.09.100
LOCARNINI, S.ZOULIM, F.: "Molecular genetics of HBV infection", ANTIVIRAL THERAPY, vol. 15, no. 3, 2010, pages 3 - 14
BARRERA, A.GUERRA, B.NOTVALL, L.LANFORD, R.E.: "Mapping of the hepatitis B virus pre-Sl domain involved in receptor recognition", JOURNAL OF VIROLOGY, vol. 79, 2005, pages 9786 - 9798, XP002490834, DOI: 10.1128/JVI.79.15.9786-9798.2005
GLEBE, D. ET AL.: "Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes", GASTROENTEROLOGY, vol. 129, 2005, pages 234 - 245, XP005313841, DOI: 10.1053/j.gastro.2005.03.090
GRIPON, P.CANNIE, I.URBAN, S.: "Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein", JOURNAL OF VIROLOGY, vol. 79, 2005, pages 1613 - 1622, XP002494027, DOI: 10.1128/JVI.79.3.1613-1622.2005
YAN, H. ET AL.: "Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus", ELIFE, vol. 1, 2012, pages e00049, XP055694013, DOI: 10.7554/eLife.00049
LE SEYEC, J.CHOUTEAU, P.CANNIE, I.GUGUEN-GUILLOUZO, C.GRIPON, P.: "Infection process of the hepatitis B virus depends on the presence of a defined sequence in the pre-Sl domain", JOURNAL OF VIROLOGY, vol. 73, 1999, pages 2052 - 2057, XP002177120
ANWER, M.S.STIEGER, B.: "Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters", PFLUGERS ARCHIV : EUROPEAN JOURNAL OF PHYSIOLOGY, vol. 466, 2014, pages 77 - 89
HAGENBUCH, B.STIEGER, B.FOGUET, M.LUBBERT, H.MEIER, P.J.: "Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 88, 1991, pages 10629 - 10633, XP002092889, DOI: 10.1073/pnas.88.23.10629
KONIG, A. ET AL.: "Kinetics of the bile acid transporter and hepatitis B virus receptor Na+/taurocholate cotransporting polypeptide (NTCP) in hepatocytes", JOURNAL OF HEPATOLOGY, vol. 61, 2014, pages 867 - 875, XP029060223, DOI: 10.1016/j.jhep.2014.05.018
YAN, H. ET AL.: "Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on sodium taurocholate cotransporting polypeptide", JOURNAL OF VIROLOGY, vol. 88, 2014, pages 3273 - 3284, XP055598830, DOI: 10.1128/JVI.03478-13
See also references of EP 3738603A4
GORDON R DREESMAN, YANUARIO SANCHEZ, IRINA IONESCU-MATIN, JAMES T. SPARROW, HOWARD R. SIX, DARRELL L. PETERSON, F. BLAINE HOLLING: "Antibody to hepatitis B surface antigen after a single inoculation of uncoupled synthetic HBsAg peptide", NATURE, vol. 295, no. 5845, 31 January 1982 (1982-01-31), pages 158 - 160, XP055722227, ISSN: 0028-0836, DOI: 10.1038/295158a0
NKONGOLO, S. ET AL.: "Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-independent interference with the NTCP receptor", JOURNAL OF HEPATOLOGY, vol. 60, 2014, pages 723 - 731, XP028632086, DOI: 10.1016/j.jhep.2013.11.022
NI, Y. ET AL.: "Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes", GASTROENTEROLOGY, vol. 146, 2014, pages 1070 - 1083
YAN H ET AL.: "Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on sodium taurocholate cotransporting polypeptide", J VIROL, vol. 88, 2014, pages 3273 - 3284, XP055598830, DOI: 10.1128/JVI.03478-13
WATASHI K ET AL.: "Interleukin-1 and tumor necrosis factor-alpha trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID", HEPATOLOGY, vol. 59, 2014, pages 1726 - 1737
BLANK A ET AL.: "The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics", CLIN PHARMACOL THER, vol. 00, 2017, pages 1 - 8
MORIMOTO, J.HAYASHI, Y.SUGA, H.: "Discovery of Macrocyclic Peptides Armed with a Mechanism-Based Warhead: Isoform-Selective Inhibition of Human Deacetylase SIRT2", ANGEW. CHEM. INT. ED. ENGL., vol. 51, 2012, pages 3423 - 3427, XP055133046, DOI: 10.1002/anie.201108118
KAWAKAMI, T.MURAKAMI, H.SUGA, H.: "Messenger RNA-programmed incorporation of multiple N-methyl-amino acids into linear and cyclic peptides", CHEM. BIOL., vol. 15, 2008, pages 32 - 42, XP022428215, DOI: 10.1016/j.chembiol.2007.12.008
GOTO, Y.KATOH, T.SUGA, H.: "Flexizymes for genetic code reprogramming", NAT. PROTOC., vol. 6, 2011, pages 779 - 790, XP009158277, DOI: 10.1038/nprot.2011.331
HAYASHI, Y.MORIMOTO, J.SUGA, H.: "In vitro selection of anti-Akt2 thioether-macrocyclic peptides leading to isoform-selective inhibitors", ACS CHEM. BIOL., vol. 7, 2012, pages 607 - 613, XP055133026, DOI: 10.1021/cb200388k
WATASHI, K. ET AL.: "Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP", HEPATOLOGY, vol. 59, 2014, pages 1726 - 1737, XP055474935, DOI: 10.1002/hep.26982
SHIMURA, S. ET AL.: "Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity", JOURNAL OF HEPATOLOGY, vol. 66, 2017, pages 685 - 692, XP029944794, DOI: 10.1016/j.jhep.2016.11.009
IWAMOTO, M. ET AL.: "Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 443, 2014, pages 808 - 813, XP028815147, DOI: 10.1016/j.bbrc.2013.12.052
OGURA, N.WATASHI, K.NOGUCHI, T.WAKITA, T.: "Formation of covalently closed circular DNA in Hep38.7-Tet cells, a tetracycline inducible hepatitis B virus expression cell line", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 452, 2014, pages 315 - 321, XP029067246, DOI: 10.1016/j.bbrc.2014.08.029
ISHIDA, Y. ET AL.: "Novel robust in vitro hepatitis B virus infection model using fresh human hepatocytes isolated from humanized mice", THE AMERICAN JOURNAL OF PATHOLOGY, vol. 185, 2015, pages 1275 - 1285
TSUKUDA, S. ET AL.: "Dysregulation of retinoic acid receptor diminishes hepatocyte permissiveness to hepatitis B virus infection through modulation of sodium taurocholate cotransporting polypeptide (NTCP) expression", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 290, 2015, pages 5673 - 5684, XP055346708, DOI: 10.1074/jbc.M114.602540
WATASHI, K. ET AL.: "Interleukin-1 and tumor necrosis factor-alpha trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 288, 2013, pages 31715 - 31727
KANEKO, M. ET AL.: "A Novel Tricyclic Polyketide, Vanitaracin A, Specifically Inhibits the Entry of Hepatitis B and D Viruses by Targeting Sodium Taurocholate Cotransporting Polypeptide", JOURNAL OF VIROLOGY, vol. 89, 2015, pages 11945 - 11953, XP055481652, DOI: 10.1128/JVI.01855-15
BARTOSCH, B.DUBUISSON, J.COSSET, F.L.: "Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes", THE JOURNAL OF EXPERIMENTAL MEDICINE, vol. 197, 2003, pages 633 - 642, XP002563514, DOI: 10.1084/jem.20021756
NAKAJIMA, S. ET AL.: "Specific inhibition of hepatitis C virus entry into host hepatocytes by fungi-derived sulochrin and its derivatives", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 440, 2013, pages 515 - 520, XP028761550, DOI: 10.1016/j.bbrc.2013.09.100
LOCARNINI, S.ZOULIM, F.: "Molecular genetics of HBV infection", ANTIVIRAL THERAPY, vol. 15, no. 3, 2010, pages 3 - 14
BARRERA, A.GUERRA, B.NOTVALL, L.LANFORD, R.E.: "Mapping of the hepatitis B virus pre-Sl domain involved in receptor recognition", JOURNAL OF VIROLOGY, vol. 79, 2005, pages 9786 - 9798, XP002490834, DOI: 10.1128/JVI.79.15.9786-9798.2005
GLEBE, D. ET AL.: "Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes", GASTROENTEROLOGY, vol. 129, 2005, pages 234 - 245, XP005313841, DOI: 10.1053/j.gastro.2005.03.090
GRIPON, P.CANNIE, I.URBAN, S.: "Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein", JOURNAL OF VIROLOGY, vol. 79, 2005, pages 1613 - 1622, XP002494027, DOI: 10.1128/JVI.79.3.1613-1622.2005
YAN, H. ET AL.: "Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus", ELIFE, vol. 1, 2012, pages e00049, XP055694013, DOI: 10.7554/eLife.00049
LE SEYEC, J.CHOUTEAU, P.CANNIE, I.GUGUEN-GUILLOUZO, C.GRIPON, P.: "Infection process of the hepatitis B virus depends on the presence of a defined sequence in the pre-Sl domain", JOURNAL OF VIROLOGY, vol. 73, 1999, pages 2052 - 2057, XP002177120
ANWER, M.S.STIEGER, B.: "Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters", PFLUGERS ARCHIV : EUROPEAN JOURNAL OF PHYSIOLOGY, vol. 466, 2014, pages 77 - 89
HAGENBUCH, B.STIEGER, B.FOGUET, M.LUBBERT, H.MEIER, P.J.: "Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 88, 1991, pages 10629 - 10633, XP002092889, DOI: 10.1073/pnas.88.23.10629
KONIG, A. ET AL.: "Kinetics of the bile acid transporter and hepatitis B virus receptor Na+/taurocholate cotransporting polypeptide (NTCP) in hepatocytes", JOURNAL OF HEPATOLOGY, vol. 61, 2014, pages 867 - 875, XP029060223, DOI: 10.1016/j.jhep.2014.05.018
YAN, H. ET AL.: "Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on sodium taurocholate cotransporting polypeptide", JOURNAL OF VIROLOGY, vol. 88, 2014, pages 3273 - 3284, XP055598830, DOI: 10.1128/JVI.03478-13
See also references of EP 3738603A4
Attorney, Agent or Firm:
INABA, Yoshiyuki et al. (JP)
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