Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C45H60ClN7O9S |
Molecular Weight | 910.517 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 8 / 8 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC[C@@H]1C[C@]1(NC(=O)[C@@H]2C[C@H](CN2C(=O)[C@@H](NC(=O)O[C@@H]3C[C@@H]4C[C@@H]4C3)C(C)(C)C)OC5=CC(=NC6=C5C=CC(OCCN7CCOCC7)=C6Cl)C8=CSC(NC(C)C)=N8)C(O)=O
InChI
InChIKey=OTXAMWFYPMNDME-FQQWJMKMSA-N
InChI=1S/C45H60ClN7O9S/c1-7-27-21-45(27,41(56)57)51-39(54)33-19-29(22-53(33)40(55)38(44(4,5)6)50-43(58)62-28-17-25-16-26(25)18-28)61-35-20-31(32-23-63-42(49-32)47-24(2)3)48-37-30(35)8-9-34(36(37)46)60-15-12-52-10-13-59-14-11-52/h8-9,20,23-29,33,38H,7,10-19,21-22H2,1-6H3,(H,47,49)(H,50,58)(H,51,54)(H,56,57)/t25-,26+,27-,28+,29-,33+,38-,45-/m1/s1
Vedroprevir, or GS-9451, is a potent inhibitor of the HCV NS3 protease (Box 1). NS3 is a serine protease that cleaves the HCV polyprotein and helps generate the viral replication complex. Through binding NS3, vedroprevir halts the assembly of the viral replication complex, thus interfering with the assembly and release of viral particles. Vedroprevir is a potent inhibitor of NS3 protease with high selectivity against off-target proteases. It has rapid association kinetics and slow dissociation kinetics. Preclinical studies of vedroprevir showed high oral bioavailability in rats, dogs, and monkeys. Preclinical studies of vedroprevir demonstrated potent NS3 inhibition using laboratory strains as well as patient-derived NS3 protease gene isolates. In a phase I, randomized trial of vedroprevir monotherapy, doses of 200 and 400 mg/day yielded median maximal HCV RNA reductions of −3.2 log10 in genotype 1a patients and −3.5 log10 in genotype 1b patients. Significantly less activity was seen against genotype 2a HCV when compared to genotype 1. Vedroprevir was not listed on the Gilead Sciences pipeline in its 2014 annual report and appears to have been discontinued for the once-daily treatment of Hepatitis C.
Originator
Approval Year
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02226549
Hepatitis C virus infection: Ledipasvir/Sofosbuvir fixed-dose combination and Vedroprevir with or without Ribavirin in treatment-experienced participants with chronic Genotype 1 HCV infection and cirrhosis:
Drug: LDV/SOF
LDV/SOF (90/400 mg) FDC tablet administered orally once daily
Drug: Vedroprevir (VDV)
VDV 80 mg tablet administered orally once daily
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25139683
Vedroprevir had measured Ki value of 410 pM, against genotype 1b NS3 protease; Ki value was higher against genotype 2a (39 nM) and genotype 3 proteases (319 nM). Selectivity of vedroprevir was >10,000-fold against all tested off-target proteases.
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NCI_THESAURUS |
C281
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NCI_THESAURUS |
C783
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C152843
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25167947
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1310824-24-8
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KGD958X2B9
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ZZ-81
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CHEMBL2013174
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9745
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DB12037
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100000174903
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1098189-15-1
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ACTIVE MOIETY