BMS-791325

Beclabuvir (BMS-791325) hydrochloride is an allosteric inhibitor that binds to thumb site 1 of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase, and inhibits recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 with IC50 of < 28 nM[1][2].

This potent allosteric inhibitor (FW = 673.87 g/mol) targets hepatitis C virus NS5B polymerase IC50 <0.5 nM (biochemical assay) and EC50 = 0.8-6 nM (replicon assay). Unlike prior cyclopropyl-fused indolobenzazepine inhibitors, BMS-791325 has improved solubility and membrane permeability properties as well as reduced off-target activities, directed most notably against human pregnane X receptor (hPXR) transactivation.

[1] Gentile I, et al. Beclabuvir for the treatment of hepatitis C. Expert Opin Investig Drugs. 2015;24(8):1111-21. DOI:10.1517/13543784.2015.1059820
[2] Tatum H, et al. A randomized, placebo-controlled study of the NS5B inhibitor beclabuvir with peginterferon/ribavirin for HCV genotype 1. J Viral Hepat. 2015 Aug;22(8):658-64. DOI:10.1111/jvh.12372