Danoprevir | CAS:850876-88-9

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Name:Danoprevir; ITMN-191; R7227; RO5190591; RG7227
Cat. No. :CS-0337
CAS No. :850876-88-9
Formula:C35H46FN5O9S
M. Wt. : 731.83
Solubility:DMSO

Danoprevir is a peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV) with IC50 of 0.2-3.5 nM. The inhibition effect on HCV genotypes 1A/1B/4/5/6 is appr 10-fold higher than 2B/3A. IC50 & Target: IC50: 0.2-3.5 nM (NS3/4A protease)In Vitro: In Huh7.5 cells transfected with chimeric recombinant virus, Danoprevir shows antiviral inhibition effects against HCV genotypes 1, 4 and 6 with IC50 of 2-3 nM, which are >100-fold lower than genotypes 2/3/5 (280-750 nM)[1]. Danoprevir (0.29 nM) inhibits the reference genotype 1 NS3/4A protease half-maximally, but a high dose of Danoprevir (10 μM) shows no appreciably inhibition in a panel of 79 proteases, ion channels, transporters, and cell surface receptors. Danoprevir remains bound to and inhibits NS3/4A for more than 5 hours after its initial association. Danoprevir (45 nM) eliminates a patient-derived HCV genotype 1b replicon from hepatocyte-derived Huh7 cells with an EC50 of 1.8 nM[2]. In HCV subgenomic replicon cell lines containing the individual mutations, V36M, R109K, and V170A substitutions confer little or no resistance to Danoprevir, but the R155K substitution confers a high level (62-fold increase) of resistance to Danoprevir[3]. In Vivo: Danoprevir (30 mg/kg, p.o.) administered to rats or monkeys shows that its concentrations in liver 12 hours after dosing exceed the Danoprevir concentration required to eliminate replicon RNA from cells[2]. 

Imhof I, et al. Genotype differences in susceptibility and resistance development of hepatitis C virus to protease inhibitors telaprevir (VX-950) and danoprevir (ITMN-191).Hepatology. 2011 Apr;53(4):1090-9. Bartels DJ, et al. Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3.4A protease inhibitors in treatment-naive subjects. J Infect Dis. 2008 Sep 15;198(6):800-7. Seiwert, Scott D., et al. Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227). Antimicrobial Agents and Chemotherapy (2008), 52(12), 4432-4441.