Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T05152
|
||||
| Former ID |
TTDI01926
|
||||
| Target Name |
Hepatitis C virus NS5B polymerase
|
||||
| Target Type |
Successful
|
||||
| Disease | HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2] | ||||
| Hepatitis virus infection [ICD9: 573.3; ICD10: K75.9] | |||||
| HCV genotypes 1-6 [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 | |||||
| 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 | [1] |
| INX-189 | Drug Info | Phase 2 | HCV infection | [2] | |
| PSI-7977 | Drug Info | Phase 2 | HCV infection | [3] | |
| VX-135 | Drug Info | Phase 2 | HCV infection | [4] | |
| Balapiravir | Drug Info | Phase 1 | HCV infection | [5] | |
| Drug 2878175 | Drug Info | Phase 1 | Hepatitis virus infection | [6] | |
| GS-6620 | Drug Info | Phase 1 | HCV infection | [7] | |
| GSK-625433 | Drug Info | Phase 1 | HCV infection | [8] | |
| MBX-700 | Drug Info | Phase 1 | HCV infection | [9] | |
| PPI-383 | Drug Info | Phase 1 | HCV infection | [10] | |
| RG-7348 | Drug Info | Phase 1 | HCV infection | [11] | |
| TMC-647055 | Drug Info | Phase 1 | HCV infection | [12] | |
| R-803 | Drug Info | Discontinued in Phase 1/2 | HCV infection | [13] | |
| JTK-109 | Drug Info | Discontinued in Phase 1 | HCV infection | [14] | |
| JTK-652 | Drug Info | Discontinued in Phase 1 | HCV infection | [15] | |
| JTK-853 | Drug Info | Discontinued in Phase 1 | HCV infection | [16] | |
| RG-7432 | Drug Info | Discontinued in Phase 1 | HCV infection | [17] | |
| GSK-2485852 | Drug Info | Terminated | HCV infection | [18] | |
| PSI-6130 | Drug Info | Terminated | HCV infection | [19] | |
| PSI-661 | Drug Info | Terminated | HCV infection | [20] | |
| Modulator | A-058 | Drug Info | [21] | ||
| antiviral polymerase inhibitors (HCV infection) | Drug Info | [21] | |||
| GS-9256 + tegobuvir | Drug Info | [21] | |||
| HCV polymerase inhibitors | Drug Info | [21] | |||
| PSI 7851 | Drug Info | ||||
| PSI-661 | Drug Info | [22] | |||
| PSI-7977 | Drug Info | [23] | |||
| R-803 | Drug Info | [24] | |||
| RG-7348 | Drug Info | [24] | |||
| Inhibitor | Balapiravir | Drug Info | [25] | ||
| Drug 2878175 | Drug Info | [26] | |||
| GS-6620 | Drug Info | [27] | |||
| GSK-2485852 | Drug Info | [28] | |||
| GSK-625433 | Drug Info | [29] | |||
| INX-189 | Drug Info | [30] | |||
| JTK-109 | Drug Info | [31] | |||
| JTK-652 | Drug Info | [32] | |||
| JTK-853 | Drug Info | [33] | |||
| MBX-700 | Drug Info | [34] | |||
| PPI-383 | Drug Info | [35] | |||
| PSI-6130 | Drug Info | [36] | |||
| RG-7432 | Drug Info | [37] | |||
| TMC-647055 | Drug Info | [38] | |||
| VX-135 | Drug Info | [39] | |||
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| DRM | DRM Info | ||||
| References | |||||
| REF 1 | 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. doi: 10.1038/nrd.2017.14. | ||||
| REF 2 | ClinicalTrials.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 3 | 2011 Pipeline of Pharmasset. | ||||
| REF 4 | ClinicalTrials.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 5 | ClinicalTrials.gov (NCT01096576) A Study of Balapiravir in Patients With Dengue Virus Infection. U.S. National Institutes of Health. | ||||
| REF 6 | ClinicalTrials.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 7 | ClinicalTrials.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 8 | ClinicalTrials.gov (NCT00439959) Monotherapy Versus Placebo Over 14 or 17 Days in Healthy and Hepatitis C Infected Adults. U.S. National Institutes of Health. | ||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037271) | ||||
| REF 10 | ClinicalTrials.gov (NCT01928147) A Phase 1a/1b Study of PPI-383 in Healthy Adults and Hepatitis C Patients. U.S. National Institutes of Health. | ||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031996) | ||||
| REF 12 | ClinicalTrials.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 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011431) | ||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018157) | ||||
| REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027431) | ||||
| REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032147) | ||||
| REF 17 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033302) | ||||
| REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024593) | ||||
| REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024904) | ||||
| REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027653) | ||||
| REF 21 | The ChEMBL database in 2017. | ||||
| REF 22 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | ||||
| REF 23 | 2013 FDA drug approvals. Nat Rev Drug Discov. 2014 Feb;13(2):85-9. | ||||
| REF 24 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | ||||
| REF 25 | R-1626, a specific oral NS5B polymerase inhibitor of hepatitis C virus. IDrugs. 2008 Oct;11(10):738-49. | ||||
| REF 26 | P1224 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 27 | Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug. Antimicrob Agents Chemother. 2014;58(4):1930-42. | ||||
| REF 28 | In vitro characterization of GSK2485852, a novel hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother. 2013 Nov;57(11):5216-24. | ||||
| REF 29 | Preclinical 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 30 | Clinical pipeline report, company report or official report of Bristol-Myers Squibb. | ||||
| REF 31 | Benzimidazole 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 32 | Safety and antiviral activity of JTK-652: a novel HCV infection inhibitor. Antivir Ther. 2010;15(5):765-73. | ||||
| REF 33 | Preclinical 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 34 | Clinical pipeline report, company report or official report of Microbiotix Inc. | ||||
| REF 35 | 1173 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 36 | An 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 37 | Chutes and Ladders in Hepatitis C Nucleoside Drug Development. Antiviral Res. 2014 February; 102: 119-147. | ||||
| REF 38 | WO patent application no. 2014,1522,75, Deuterium modified derivatives of the ns5b polymerase inhibitor tmc647055. | ||||
| REF 39 | All-oral HCV therapies near approval. Nat Rev Drug Discov. 2013 Jun;12(6):409-11. doi: 10.1038/nrd4036. | ||||
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