Target Information
Target General Information | Top | |||||
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Target ID |
T05152
(Former ID: TTDI01926)
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Target Name |
Hepatitis C virus RNA-directed RNA polymerase (HCV NS5B)
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Synonyms |
HCV NS5B; HCV p68
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Gene Name |
HCV NS5B
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Hepatitis virus infection [ICD-11: 1E50-1E51] | |||||
Function |
Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).
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BioChemical Class |
Peptidase
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UniProt ID | ||||||
EC Number |
EC 2.7.7.48
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Sequence |
SMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTSRSACQRQKKVTFDRLQVL
DSHYQDVLKEVKAAASKVKANLLSVEEACSLTPPHSAKSKFGYGAKDVRCHARKAVTHIN SVWKDLLEDNVTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVT KLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIY QCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKAR AACRAAGLQDCTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDL ELITSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFAPTLW ARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPG EINRVAACLRKLGVPPLRAWRHRARSVRARLLARGGRAAICGKYLFNWAVRTKLKLTPIA AAGQLDLSGWFTAGYSGGDIYHSVSHARPRWIWFCLLLLAAGVGIYLLPNR Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
1 | PSI-7977 | Drug Info | Approved | HCV 1-6 infection | [2] | |
2 | Sofosbuvir + velpatasvir + voxilaprevir | Drug Info | Approved | Hepatitis C virus infection | [3] | |
Clinical Trial Drug(s) | [+] 29 Clinical Trial Drugs | + | ||||
1 | BI 207127 | Drug Info | Phase 2 | Hepatitis C virus infection | [4], [5] | |
2 | BMS 791325 | Drug Info | Phase 2 | Hepatitis C virus infection | [6] | |
3 | Filibuvir | Drug Info | Phase 2 | Hepatitis C virus infection | [7] | |
4 | INX-189 | Drug Info | Phase 2 | Hepatitis C virus infection | [8] | |
5 | Setrobuvir | Drug Info | Phase 2 | Hepatitis C virus infection | [9] | |
6 | Tegobuvir | Drug Info | Phase 2 | Hepatitis C virus infection | [10] | |
7 | Valopicitabine dihydrochloride | Drug Info | Phase 2 | Virus infection | [11] | |
8 | VX-135 | Drug Info | Phase 2 | Hepatitis C virus infection | [12] | |
9 | VX-222 | Drug Info | Phase 2 | Hepatitis C virus infection | [13] | |
10 | VX-759 | Drug Info | Phase 2 | Hepatitis C virus infection | [13] | |
11 | AT-777 | Drug Info | Phase 1/2 | Hepatitis C | [14] | |
12 | A-837093 | Drug Info | Phase 1 | Hepatitis C virus infection | [15] | |
13 | ABT-072 | Drug Info | Phase 1 | Hepatitis C virus infection | [16] | |
14 | ABT-333 | Drug Info | Phase 1 | Hepatitis C virus infection | [16] | |
15 | AT-787 | Drug Info | Phase 1 | Hepatitis C | [17] | |
16 | Balapiravir | Drug Info | Phase 1 | Hepatitis C virus infection | [18] | |
17 | CC-31244 | Drug Info | Phase 1 | Hepatitis C virus infection | [19] | |
18 | Drug 2878175 | Drug Info | Phase 1 | Hepatitis virus infection | [20] | |
19 | GS-6620 | Drug Info | Phase 1 | Hepatitis C virus infection | [21] | |
20 | GSK-625433 | Drug Info | Phase 1 | Hepatitis C virus infection | [22] | |
21 | IDX-189 | Drug Info | Phase 1 | Hepatitis C virus infection | [23] | |
22 | MBX-700 | Drug Info | Phase 1 | Hepatitis C virus infection | [24] | |
23 | MK-3281 | Drug Info | Phase 1 | Hepatitis C virus infection | [25] | |
24 | PPI-383 | Drug Info | Phase 1 | Hepatitis C virus infection | [26] | |
25 | PSI-938 | Drug Info | Phase 1 | Hepatitis C virus infection | [27] | |
26 | RG-7348 | Drug Info | Phase 1 | Hepatitis C virus infection | [28] | |
27 | TMC-647055 | Drug Info | Phase 1 | Hepatitis C virus infection | [29] | |
28 | TMC649128 | Drug Info | Phase 1 | Hepatitis C virus infection | [30] | |
29 | VX-916 | Drug Info | Phase 1 | Hepatitis C virus infection | [13] | |
Discontinued Drug(s) | [+] 13 Discontinued Drugs | + | ||||
1 | HCV-796 | Drug Info | Discontinued in Phase 2 | Hepatitis C virus infection | [15] | |
2 | IDX375 | Drug Info | Discontinued in Phase 2 | Hepatitis C virus infection | [31] | |
3 | R7128 | Drug Info | Discontinued in Phase 2 | Hepatitis C virus infection | [32] | |
4 | R-803 | Drug Info | Discontinued in Phase 1/2 | Hepatitis C virus infection | [33] | |
5 | AG-021541 | Drug Info | Discontinued in Phase 1 | Hepatitis C virus infection | [15] | |
6 | HCV-086 | Drug Info | Discontinued in Phase 1 | Hepatitis virus infection | [34] | |
7 | JTK-109 | Drug Info | Discontinued in Phase 1 | Hepatitis C virus infection | [35] | |
8 | JTK-652 | Drug Info | Discontinued in Phase 1 | Hepatitis C virus infection | [36] | |
9 | JTK-853 | Drug Info | Discontinued in Phase 1 | Hepatitis C virus infection | [37] | |
10 | RG-7432 | Drug Info | Discontinued in Phase 1 | Hepatitis C virus infection | [38] | |
11 | GSK-2485852 | Drug Info | Terminated | Hepatitis C virus infection | [39] | |
12 | PSI-6130 | Drug Info | Terminated | Hepatitis C virus infection | [40] | |
13 | PSI-661 | Drug Info | Terminated | Hepatitis C virus infection | [41] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 8 Modulator drugs | + | ||||
1 | PSI-7977 | Drug Info | [1] | |||
2 | Valopicitabine dihydrochloride | Drug Info | [43] | |||
3 | RG-7348 | Drug Info | [53] | |||
4 | R-803 | Drug Info | [53] | |||
5 | PSI-661 | Drug Info | [66] | |||
6 | A-058 | Drug Info | [67] | |||
7 | GS-9256 + tegobuvir | Drug Info | [67] | |||
8 | PSI 7851 | Drug Info | [68] | |||
Inhibitor | [+] 39 Inhibitor drugs | + | ||||
1 | Sofosbuvir + velpatasvir + voxilaprevir | Drug Info | [3] | |||
2 | BI 207127 | Drug Info | [4] | |||
3 | BMS 791325 | Drug Info | [6] | |||
4 | Filibuvir | Drug Info | [7] | |||
5 | INX-189 | Drug Info | [42] | |||
6 | Setrobuvir | Drug Info | [9] | |||
7 | Tegobuvir | Drug Info | [10] | |||
8 | VX-135 | Drug Info | [44] | |||
9 | VX-222 | Drug Info | [13] | |||
10 | VX-759 | Drug Info | [13] | |||
11 | AT-777 | Drug Info | [17] | |||
12 | A-837093 | Drug Info | [15], [45] | |||
13 | ABT-072 | Drug Info | [16] | |||
14 | ABT-333 | Drug Info | [16] | |||
15 | AT-787 | Drug Info | [17] | |||
16 | Balapiravir | Drug Info | [46] | |||
17 | CC-31244 | Drug Info | [47] | |||
18 | Drug 2878175 | Drug Info | [48] | |||
19 | GS-6620 | Drug Info | [49] | |||
20 | GSK-625433 | Drug Info | [50] | |||
21 | IDX-189 | Drug Info | [23] | |||
22 | MBX-700 | Drug Info | [51] | |||
23 | MK-3281 | Drug Info | [25] | |||
24 | PPI-383 | Drug Info | [52] | |||
25 | PSI-938 | Drug Info | [27] | |||
26 | TMC-647055 | Drug Info | [54] | |||
27 | TMC649128 | Drug Info | [30] | |||
28 | VX-916 | Drug Info | [13] | |||
29 | HCV-796 | Drug Info | [15] | |||
30 | IDX375 | Drug Info | [55], [56] | |||
31 | R7128 | Drug Info | [57] | |||
32 | AG-021541 | Drug Info | [15], [58] | |||
33 | HCV-086 | Drug Info | [59] | |||
34 | JTK-109 | Drug Info | [60] | |||
35 | JTK-652 | Drug Info | [61] | |||
36 | JTK-853 | Drug Info | [62] | |||
37 | RG-7432 | Drug Info | [63] | |||
38 | GSK-2485852 | Drug Info | [64] | |||
39 | PSI-6130 | Drug Info | [65] |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: (11s)-10-[(2,5-Dimethyl-1,3-Oxazol-4-Yl)carbonyl]-11-{2-Fluoro-4-[(2-Methylprop-2-En-1-Yl)oxy]phenyl}-3,3-Dimethyl-2,3,4,5,10,11-Hexahydrothiopyrano[3,2-B][1,5]benzodiazepin-6-Ol 1,1-Dioxide | Ligand Info | |||||
Structure Description | HCV NS5B genotype 1a in complex with 1,5 benzodiazepine inhibitor 6 | PDB:3HKW | ||||
Method | X-ray diffraction | Resolution | 1.55 Å | Mutation | No | [69] |
PDB Sequence |
SMSYSWTGAL
10 VTPCAAEEQK20 LPINALSNSL30 LRHHNMVYST40 TSRSACQRQK50 KVTFDRLQVL 60 DSHYQDVLKE70 VKAAASKVKA80 NLLSVEEACS90 LTPPHSARSK100 FGYGAKDVRC 110 HARKAVTHIN120 SVWKDLLEDS130 VTPIDTTIMA140 KNEVFCVQPG152 GRKPARLIVF 162 PDLGVRVCEK172 MALYDVVSKL182 PQAVMGSSYG192 FQYSPGQRVE202 FLVQAWKSKK 212 SPMGFSYDTR222 CFDSTVTESD232 IRTEEAIYQC242 CDLDPQARVA252 IKSLTERLYV 262 GGPLTNSKGE272 NCGYRRCRAS282 GVLTTSCGNT292 LTCYIKARAA302 CRAAGLQDCT 312 MLVCGDDLVV322 ICESAGVQED332 AASLRAFTEA342 MTRYSAPPGD352 PPQPEYDLEL 362 ITSCSSNVSV372 AHDGAGKRVY382 YLTRDPTTPL392 ARAAWETARH402 TPVNSWLGNI 412 IMFAPTLWAR422 MILMTHFFSV432 LIARDQLEQA442 LDCEIYGACY452 SIEPLDLPPI 462 IQRLHGLSAF472 SLHSYSPGEI482 NRVAACLRKL492 GVPPLRAWRH502 RARSVRAKLL 512 SRGGRAAICG522 KYLFNWAVRT532 KLKLTPIAAA542 GQLDLSGWFT552 AGYSGGDIYH 562 S
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ARG158
4.531
PHE193
3.323
PRO197
3.997
ARG200
3.702
CYS316
4.936
SER365
4.747
CYS366
3.462
SER367
2.671
SER368
3.711
LEU384
3.894
ARG386
3.517
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Ligand Name: N-[(2s)-Butan-2-Yl]-6-[(3r)-3-{[4-(Trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(Trifluoromethoxy)phenyl]sulfonyl}piperazin-1-Yl]pyridazine-3-Carboxamide | Ligand Info | |||||
Structure Description | Crystal structure of the hepatitis C virus NS5B RNA-dependent RNA polymerase genotype 1a complex with N-[(2S)-butan-2-yl]-6-[(3R)-3-{[4-(trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(trifluoromethoxy)phenyl]sulfonyl}piperazin-1-yl]pyridazine-3-carboxamide | PDB:3QGI | ||||
Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [70] |
PDB Sequence |
SMSYSWTGAL
10 VTPCAAEEQK20 LPINALSNSL30 LRHHNLVYST40 TSRSACQRQK50 KVTFDRLQVL 60 DSHYQDVLKE70 VKAAASKVKA80 NLLSVEEACS90 LTPPHSAKSK100 FGYGAKDVRC 110 HARKAVAHIN120 SVWKDLLEDS130 VTPIDTTIMA140 KNEVFCVQPE150 KRKPARLIVF 162 PDLGVRVCEK172 MALYDVVSKL182 PLAVMGSSYG192 FQYSPGQRVE202 FLVQAWKSKK 212 TPMGFSYDTR222 CFDSTVTESD232 IRTEEAIYQC242 CDLDPQARVA252 IKSLTERLYV 262 GGPLTNSRGE272 NCGYRRCRAS282 GVLTTSCGNT292 LTCYIKARAA302 CRAAGLQDCT 312 MLVCGDDLVV322 ICESAGVQED332 AASLRAFTEA342 MTRYSAPPGD352 PPQPEYDLEL 362 ITSCSSNVSV372 AHDGAGKRVY382 YLTRDPTTPL392 ARAAWETARH402 TPVNSWLGNI 412 IMFAPTLWAR422 MILMTHFFSV432 LIARDQLEQA442 LNCEIYGACY452 SIEPLDLPPI 462 IQRLHGLSAF472 SLHSYSPGEI482 NRVAACLRKL492 GVPPLRAWRH502 RARSVRARLL 512 SRGGRAAICG522 KYLFNWAVRT532 KLKLTPIAAA542 GRLDLSGWFT552 AGYSGGDIYH 562 S
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VAL179
3.188
SER180
4.365
PRO183
4.413
TYR191
3.295
GLY192
3.638
PHE193
3.410
TYR195
2.986
SER196
3.247
PRO197
3.375
ARG200
3.651
SER288
2.807
CYS289
3.804
THR292
4.114
CYS316
4.449
CYS366
3.825
SER368
3.010
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Click to View More Binding Site Information of This Target with Different Ligands |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Profiles in Patients | Top | |||||
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Drug Resistance Mutation (DRM) |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651. | |||||
REF 2 | 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. | |||||
REF 3 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
REF 4 | 2011 Pipeline of Boehringer Ingelheim Pharma. | |||||
REF 5 | Open-label phase 2 study of faldaprevir, deleobuvir and ribavirin in Japanese treatment-naive patients with chronic hepatitis C virus genotype 1 in... Hepatol Res. 2016 Mar;46(3):E189-93. | |||||
REF 6 | 2011 Pipeline of Bristol-Myers Squibb. | |||||
REF 7 | Clinical pipeline report, company report or official report of Pfizer (2011). | |||||
REF 8 | 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 9 | Clinical pipeline report, company report or official report of Anadys Pharmaceuticals (2011). | |||||
REF 10 | Clinical pipeline report, company report or official report of Gilead (2011). | |||||
REF 11 | ClinicalTrials.gov (NCT00395421) Study to Evaluate Drug-drug Interaction Between Valopicitabine and Ribavirin. U.S. National Institutes of Health. | |||||
REF 12 | 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 13 | 2011 Pipeline of Vertex. | |||||
REF 14 | ClinicalTrials.gov (NCT04309734) Study of AT-777 in Healthy Subjects and AT-777 in Combination With AT-527 in HCV-Infected Subjects. U.S. National Institutes of Health. | |||||
REF 15 | Emerging drugs for hepatitis C. Expert Opin Emerg Drugs. 2008 Mar;13(1):1-19. | |||||
REF 16 | Clinical pipeline report, company report or official report of Abbott Laboratories (2011) | |||||
REF 17 | Clinical pipeline report, company report or official report of Atea Pharmaceuticals. | |||||
REF 18 | ClinicalTrials.gov (NCT01096576) A Study of Balapiravir in Patients With Dengue Virus Infection. U.S. National Institutes of Health. | |||||
REF 19 | ClinicalTrials.gov (NCT02760758) A Study of CDI-31244: A Novel NNI in HV and HCV Infected Subjects. U.S. National Institutes of Health. | |||||
REF 20 | 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 21 | 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 22 | 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 23 | Clinical pipeline report, company report or official report of Idenix (2011). | |||||
REF 24 | 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 25 | Clinical pipeline report, company report or official report of Merck (2011). | |||||
REF 26 | 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 27 | 2011 Pipeline of Pharmasset. | |||||
REF 28 | 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 29 | 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 30 | Clinical pipeline report, company report or official report of Medivir (2011). | |||||
REF 31 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031314) | |||||
REF 32 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025214) | |||||
REF 33 | 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 34 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020428) | |||||
REF 35 | 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 36 | 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 37 | 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 38 | 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 39 | 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 40 | 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 41 | 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 42 | Clinical pipeline report, company report or official report of Bristol-Myers Squibb. | |||||
REF 43 | Valopicitabine dihydrochloride:a specific polymerase inhibitor of hepatitis C virus. Curr Opin Investig Drugs. 2007 Feb;8(2):150-8. | |||||
REF 44 | All-oral HCV therapies near approval. Nat Rev Drug Discov. 2013 Jun;12(6):409-11. | |||||
REF 45 | Activity of a potent hepatitis C virus polymerase inhibitor in the chimpanzee model. Antimicrob Agents Chemother. 2007 Dec;51(12):4290-6. | |||||
REF 46 | R-1626, a specific oral NS5B polymerase inhibitor of hepatitis C virus. IDrugs. 2008 Oct;11(10):738-49. | |||||
REF 47 | Clinical pipeline report, company report or official report of Cocrystal Pharma. | |||||
REF 48 | 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 49 | Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug. Antimicrob Agents Chemother. 2014;58(4):1930-42. | |||||
REF 50 | 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 51 | Clinical pipeline report, company report or official report of Microbiotix Inc. | |||||
REF 52 | 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 53 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
REF 54 | WO patent application no. 2014,1522,75, Deuterium modified derivatives of the ns5b polymerase inhibitor tmc647055. | |||||
REF 55 | Therapy with amineptine, a dopamine reuptake inhibitor, in patients with major depression. Indian J Psychiatry. 1997 Apr;39(2):147-53. | |||||
REF 56 | Clinical pipeline report, company report or official report of Idenix (2009). | |||||
REF 57 | Clinical pipeline report, company report or official report of Roche (2009). | |||||
REF 58 | In vitro resistance study of AG-021541, a novel nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. Antimicrob Agents Chemother. 2008 Feb;52(2):675-83. | |||||
REF 59 | Challenges and successes in developing new therapies for hepatitis C. Nature. 2005 Aug 18;436(7053):953-60. | |||||
REF 60 | 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 61 | Safety and antiviral activity of JTK-652: a novel HCV infection inhibitor. Antivir Ther. 2010;15(5):765-73. | |||||
REF 62 | 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 63 | Chutes and Ladders in Hepatitis C Nucleoside Drug Development. Antiviral Res. 2014 February; 102: 119-147. | |||||
REF 64 | In vitro characterization of GSK2485852, a novel hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother. 2013 Nov;57(11):5216-24. | |||||
REF 65 | 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 66 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
REF 67 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. | |||||
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