HCV protease inhibitor
Danoprevir (ITMN-191) is a peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV) with IC50 of 0.2-3.5 nM, inhibition effect for HCV genotypes 1A/1B/4/5/6 is ~10-fold higher than 2B/3A. Phase 2.
Danoprevir (ITMN-191) 5 mg
£208.00
Target: HCV NS3/4A protease 0.2 nM-3.5 nM
Chemical name: 2H-Isoindole-2-carboxylic acid, 4-fluoro-1,3-dihydro-, (2R,6S,13aS,14aR,16aS)-14a-[[(cyclopropylsulfonyl)amino]carbonyl]-6-[[(1,1-dimethylethoxy)carbonyl]amino]-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydro-5,16-dioxocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-2-yl ester
Formula: C35H46FN5O9S
Molecular weight: 731.83
Purity: 95.40 % (HPLC)
Solubility: 144 mg/mL (DMSO), 144 mg/mL (ethanol)
Size: 5 mg
Storage: 3 years -20°C powder, 2 years -80°C in solvent
In vitro:
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. [1] 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. [2] 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). [3]
In vivo: Danoprevir (30 mg/kg) 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. [1]
A peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV).
References:
[1] Seiwert SD, et al. Antimicrob Agents Chemother, 2008, 52(12), 4432-4441.
[2] Bartels DJ, et al. J Infect Dis, 2008, 198(6), 800-807.
[3] Imhof I, et al. Hepatology, 2011, 53(4), 1090-1099.