Target Information

Target General Infomation
Target ID
T05152
Former ID
TTDI01926
Target Name
Hepatitis C virus NS5B polymerase
Target Type
Successful
Disease Hepatitis virus infection [ICD9: 573.3; ICD10: K75.9]
HCV genotypes 1-6 [ICD10: B17.1, B18.2]
HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2]
Unspecified [ICD code not available]
Function
NS5B is an RNA-dependent RNA polymerase that plays an essential role in the virus replication.
UniProt ID
P26664 (2421-3011)
Sequence
SMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTSRSACQRQKKVTFDRLQVL
DSHYQDVLKEVKAAASKVKANLLSVEEACSLTPPHSAKSKFGYGAKDVRCHARKAVTHIN
SVWKDLLEDNVTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVT
KLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIY
QCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKAR
AACRAAGLQDCTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDL
ELITSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFAPTLW
ARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPG
EINRVAACLRKLGVPPLRAWRHRARSVRARLLARGGRAAICGKYLFNWAVRTKLKLTPIA
AAGQLDLSGWFTAGYSGGDIYHSVSHARPRWIWFCLLLLAAGVGIYLLPNR
Drugs and Mode of Action
Drug(s) PSI-7977 Drug Info Approved HCV genotypes 1-6 [889440]
INX-189 Drug Info Phase 2 HCV infection [523604]
PSI-7977 Drug Info Phase 2 HCV infection [551499]
VX-135 Drug Info Phase 2 HCV infection [524122]
Balapiravir Drug Info Phase 1 HCV infection [522994]
Drug 2878175 Drug Info Phase 1 Hepatitis virus infection [524572]
GS-6620 Drug Info Phase 1 HCV infection [523396]
GSK-625433 Drug Info Phase 1 HCV infection [521970]
MBX-700 Drug Info Phase 1 HCV infection [549438]
PPI-383 Drug Info Phase 1 HCV infection [524411]
RG-7348 Drug Info Phase 1 HCV infection [549078]
TMC-647055 Drug Info Phase 1 HCV infection [523173]
R-803 Drug Info Discontinued in Phase 1/2 HCV infection [546948]
JTK-109 Drug Info Discontinued in Phase 1 HCV infection [547651]
JTK-652 Drug Info Discontinued in Phase 1 HCV infection [548657]
JTK-853 Drug Info Discontinued in Phase 1 HCV infection [549089]
RG-7432 Drug Info Discontinued in Phase 1 HCV infection [549178]
GSK-2485852 Drug Info Terminated HCV infection [548323]
PSI-6130 Drug Info Terminated HCV infection [548353]
PSI-661 Drug Info Terminated HCV infection [548684]
Modulator A-058 Drug Info [1572605]
antiviral polymerase inhibitors (HCV infection) Drug Info [1572605]
GS-9256 + tegobuvir Drug Info [1572605]
HCV polymerase inhibitors Drug Info [1572605]
PSI 7851 Drug Info
PSI-661 Drug Info [556264]
PSI-7977 Drug Info [532651]
R-803 Drug Info [1572591]
RG-7348 Drug Info [1572591]
Inhibitor Balapiravir Drug Info [529730]
Drug 2878175 Drug Info [551640]
GS-6620 Drug Info [532625]
GSK-2485852 Drug Info [532455]
GSK-625433 Drug Info [544077]
INX-189 Drug Info [550009]
JTK-109 Drug Info [528324]
JTK-652 Drug Info [531105]
JTK-853 Drug Info [544247]
MBX-700 Drug Info [551151]
PPI-383 Drug Info [551639]
PSI-6130 Drug Info [530284]
RG-7432 Drug Info [544368]
TMC-647055 Drug Info [550180]
VX-135 Drug Info [525394]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
DRM DRM Info
References
Ref 521970ClinicalTrials.gov (NCT00439959) Monotherapy Versus Placebo Over 14 or 17 Days in Healthy and Hepatitis C Infected Adults. U.S. National Institutes of Health.
Ref 522994ClinicalTrials.gov (NCT01096576) A Study of Balapiravir in Patients With Dengue Virus Infection. U.S. National Institutes of Health.
Ref 523173ClinicalTrials.gov (NCT01202825) TMC647055HPC1001 - First-in-human Trial to Examine Safety, Tolerability and Pharmacokinetics (How the Drug is Absorbed Into the Bloodstream) of Increasing Single OralDoses and of Increasing Repeated Oral Doses of TMC647055 in Healthy Volunteers and in Hepatitis C Virus Infected Patients. U.S. National Institutes of Health.
Ref 523396ClinicalTrials.gov (NCT01316237) A Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-6620 in Treatment Naive Subjects With Chronic Hepatitis C Virus Infection. U.S. National Institutes of Health.
Ref 523604ClinicalTrials.gov (NCT01425970) Chronically-infected HCV Genotype 2 and 3 Treatment-naive Subjects: Part A: Safety and Efficacy of INX-08189 With Peg IFN Alfa-2a and Ribavirin. Part B: INX-08189 in Interferon Free Treatment With Daclatasvir and/or Ribavirin. U.S. National Institutes of Health.
Ref 524122ClinicalTrials.gov (NCT01726946) A Phase 2 Study to Evaluate the Safety and Efficacy of VX-135 With Ribavirin in Treatment-Naive Subjects With Chronic Hepatitis C. U.S. National Institutes of Health.
Ref 524411ClinicalTrials.gov (NCT01928147) A Phase 1a/1b Study of PPI-383 in Healthy Adults and Hepatitis C Patients. U.S. National Institutes of Health.
Ref 524572ClinicalTrials.gov (NCT02014571) Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of Repeat Doses of GSK2878175 in Subjects With Chronic Hepatitis C.. U.S. National Institutes of Health.
Ref 546948Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011431)
Ref 547651Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018157)
Ref 548323Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024593)
Ref 548353Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024904)
Ref 548657Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027431)
Ref 548684Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027653)
Ref 549078Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031996)
Ref 549089Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032147)
Ref 549178Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033302)
Ref 549438Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037271)
Ref 5514992011 Pipeline of Pharmasset.
Ref 8894402016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. doi: 10.1038/nrd.2017.14.
Ref
Ref 525394All-oral HCV therapies near approval. Nat Rev Drug Discov. 2013 Jun;12(6):409-11. doi: 10.1038/nrd4036.
Ref 528324Benzimidazole derivatives bearing substituted biphenyls as hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors: structure-activity relationship studies and identification of a potent and highly selective inhibitor JTK-109. J Med Chem. 2006 Jul 27;49(15):4721-36.
Ref 529730R-1626, a specific oral NS5B polymerase inhibitor of hepatitis C virus. IDrugs. 2008 Oct;11(10):738-49.
Ref 530284An efficient and diastereoselective synthesis of PSI-6130: a clinically efficacious inhibitor of HCV NS5B polymerase. J Org Chem. 2009 Sep 4;74(17):6819-24.
Ref 531105Safety and antiviral activity of JTK-652: a novel HCV infection inhibitor. Antivir Ther. 2010;15(5):765-73.
Ref 532455In vitro characterization of GSK2485852, a novel hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother. 2013 Nov;57(11):5216-24.
Ref 532625Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug. Antimicrob Agents Chemother. 2014;58(4):1930-42.
Ref 5326512013 FDA drug approvals. Nat Rev Drug Discov. 2014 Feb;13(2):85-9.
Ref 544077Preclinical Characterization of PF-00868554, a Potent Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase . Antimicrob Agents Chemother. 2009 June; 53(6): 2544-2552.
Ref 544247Preclinical Characterization of JTK-853, a Novel Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase. Antimicrob Agents Chemother. 2012 August; 56(8): 4250-4256.
Ref 544368Chutes and Ladders in Hepatitis C Nucleoside Drug Development. Antiviral Res. 2014 February; 102: 119-147.
Ref 550009Clinical pipeline report, company report or official report of Bristol-Myers Squibb.
Ref 550180WO patent application no. 2014,1522,75, Deuterium modified derivatives of the ns5b polymerase inhibitor tmc647055.
Ref 551151Clinical pipeline report, company report or official report of Microbiotix Inc.
Ref 5516391173 IDENTIFICATION AND CHARACTERIZATION OF PPI-383, A NEXT GENERATION HCV NS5B NON-NUCLEOSIDE INHIBITOR WITH POTENT ACTIVITY AGAINST ALL MAJOR HCV GENOTYPES. Journal of Hepatology Volume 56, Supplement 2, April 2012, Pages S464.
Ref 551640P1224 GSK2878175, A POTENT NON-NUCLEOSIDE INHIBITOR OF HCV NS5B WITH PAN-GENOTYPIC ACTIVITY. Journal of Hepatology Volume 60, Issue 1, Supplement, April 2014, Pages S496.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
Ref 1572605The ChEMBL database in 2017.

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