Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMVBWH)

DTT Name Hepatitis C virus RNA-directed RNA polymerase (HCV NS5B)
Synonyms HCV NS5B; HCV p68
Gene Name HCV NS5B
DTT Type
Successful target
 [1]
BioChemical Class
Peptidase
UniProt ID
POLG_HCV1
TTD ID
T05152
EC Number
EC 2.7.7.48
Sequence
SMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTSRSACQRQKKVTFDRLQVL
DSHYQDVLKEVKAAASKVKANLLSVEEACSLTPPHSAKSKFGYGAKDVRCHARKAVTHIN
SVWKDLLEDNVTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVT
KLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGFSYDTRCFDSTVTESDIRTEEAIY
QCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCRASGVLTTSCGNTLTCYIKAR
AACRAAGLQDCTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDL
ELITSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFAPTLW
ARMILMTHFFSVLIARDQLEQALDCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPG
EINRVAACLRKLGVPPLRAWRHRARSVRARLLARGGRAAICGKYLFNWAVRTKLKLTPIA
AAGQLDLSGWFTAGYSGGDIYHSVSHARPRWIWFCLLLLAAGVGIYLLPNR
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).

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PSI-7977 DMLSUWZ HCV 1-6 infection 1E51 Approved [1]
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29 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
BI 207127 DMMSGAT Hepatitis C virus infection 1E51.1 Phase 2 [2]
BMS 791325 DMKH4PI Hepatitis C virus infection 1E51.1 Phase 2 [3]
Filibuvir DMNSYXB Hepatitis C virus infection 1E51.1 Phase 2 [4]
INX-189 DMSTJ6Q Hepatitis C virus infection 1E51.1 Phase 2 [5]
Setrobuvir DMTNDM2 Hepatitis C virus infection 1E51.1 Phase 2 [6]
Tegobuvir DM6YI5T Hepatitis C virus infection 1E51.1 Phase 2 [7]
Valopicitabine dihydrochloride DMFWZ2U Virus infection 1A24-1D9Z Phase 2 [8]
VX-135 DMZ3FE8 Hepatitis C virus infection 1E51.1 Phase 2 [9]
VX-222 DMO3U4W Hepatitis C virus infection 1E51.1 Phase 2 [10]
VX-759 DMJUSM8 Hepatitis C virus infection 1E51.1 Phase 2 [10]
AT-777 DM7O89Q Hepatitis C 1E51 Phase 1/2 [11]
A-837093 DMX0JLI Hepatitis C virus infection 1E51.1 Phase 1 [12]
ABT-072 DMG4H9Y Hepatitis C virus infection 1E51.1 Phase 1 [13]
ABT-333 DM7TOWX Hepatitis C virus infection 1E51.1 Phase 1 [13]
AT-787 DMHYO38 Hepatitis C 1E51 Phase 1 [11]
Balapiravir DMAJPOX Hepatitis C virus infection 1E51.1 Phase 1 [14]
CC-31244 DMAYHT4 Hepatitis C virus infection 1E51.1 Phase 1 [15]
Drug 2878175 DMNFEC6 Hepatitis virus infection 1E50-1E51 Phase 1 [16]
GS-6620 DMRDNPC Hepatitis C virus infection 1E51.1 Phase 1 [17]
GSK-625433 DM7CIN4 Hepatitis C virus infection 1E51.1 Phase 1 [18]
IDX-189 DMYG3PZ Hepatitis C virus infection 1E51.1 Phase 1 [19]
MBX-700 DMTXIZ1 Hepatitis C virus infection 1E51.1 Phase 1 [20]
MK-3281 DMG0Q27 Hepatitis C virus infection 1E51.1 Phase 1 [21]
PPI-383 DMEOJUN Hepatitis C virus infection 1E51.1 Phase 1 [22]
PSI-938 DM5ZR4Q Hepatitis C virus infection 1E51.1 Phase 1 [23]
RG-7348 DMFDKS7 Hepatitis C virus infection 1E51.1 Phase 1 [24]
TMC-647055 DMYEALO Hepatitis C virus infection 1E51.1 Phase 1 [25]
TMC649128 DMAOV7M Hepatitis C virus infection 1E51.1 Phase 1 [26]
VX-916 DMAJ2T4 Hepatitis C virus infection 1E51.1 Phase 1 [10]
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⏷ Show the Full List of 29 Clinical Trial Drug(s)
13 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
HCV-796 DMPQSE4 Hepatitis C virus infection 1E51.1 Discontinued in Phase 2 [12]
IDX375 DMRPBJW Hepatitis C virus infection 1E51.1 Discontinued in Phase 2 [27]
R7128 DM9BI3Y Hepatitis C virus infection 1E51.1 Discontinued in Phase 2 [28]
R-803 DMRQPOD Hepatitis C virus infection 1E51.1 Discontinued in Phase 1/2 [24]
AG-021541 DM1TYM4 Hepatitis C virus infection 1E51.1 Discontinued in Phase 1 [12]
HCV-086 DM2RF06 Hepatitis virus infection 1E50-1E51 Discontinued in Phase 1 [29]
JTK-109 DMUNYR7 Hepatitis C virus infection 1E51.1 Discontinued in Phase 1 [30]
JTK-652 DMZFEY1 Hepatitis C virus infection 1E51.1 Discontinued in Phase 1 [31]
JTK-853 DM64FX9 Hepatitis C virus infection 1E51.1 Discontinued in Phase 1 [32]
RG-7432 DMSUV3B Hepatitis C virus infection 1E51.1 Discontinued in Phase 1 [33]
GSK-2485852 DMOALVR Hepatitis C virus infection 1E51.1 Terminated [34]
PSI-6130 DMWUOA8 Hepatitis C virus infection 1E51.1 Terminated [35]
PSI-661 DM579WS Hepatitis C virus infection 1E51.1 Terminated [36]
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⏷ Show the Full List of 13 Discontinued Drug(s)
2 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
A-058 DMHSPRE Hepatitis C virus infection 1E51.1 Investigative [37]
PSI 7851 DM5ZU1V Hepatitis C virus infection 1E51.1 Investigative [38]
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