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Bioorg Med Chem Lett. 2019 May 4. pii: S0960-894X(19)30248-3. doi: 10.1016/j.bmcl.2019.04.027. [Epub ahead of print]

Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®.

Author information

1
Medicinal Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States. Electronic address: john.link@gilead.com.
2
Medicinal Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.
3
Drug Metabolism, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.
4
Biology, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.
5
Formulation and Process Development, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.
6
Structural Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.

Abstract

Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa®, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi®, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.

KEYWORDS:

DAA; Direct-acting-antiviral; Epclusa(®); GS-5816; HCV; Hepatitis C Virus; NS5A; Non-structural protein 5A; Rule-of-five; SVR; Single-tablet regimen; Sofosbuvir; Sustained viral response; Velpatasvir

PMID:
31230974
DOI:
10.1016/j.bmcl.2019.04.027

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