Asunaprevir_product_DataBase

Bioactivity

Asunaprevir (BMS-650032) is a potent and orally bioavailable hepatitis C virus (HCV) NS3 protease inhibitor, with IC50 of 0.2 nM-3.5 nM[1]. Asunaprevir inhibits SARS-CoV-2 3CLpro activity[5].

Target

IC50: 0.2 nM-3.5 nM (HCV NS3 protease)

Invitro

In multiple experiments, populations of resistant colonies are markedly reduced when cells are treated with a combination of DCV and Asunaprevir[1]. Asunaprevir (ASV) inhibits the NS3 proteolytic activity of genotype 1a (H77 strain) and genotype 1b (J4L6S strain), with IC50s of 0.7 and 0.3 nM, respectively. The EC50s of ASV against replicons encoding the NS3 protease domains representing genotypes 1a, 1b, and 4a, range from 1.2 to 4.0 nM[2]. Replicon cells are maintained under selective pressure with asunaprevir at concentrations of 10 and 30 times the EC50 values (50 or 150 nM final concentrations, respectively). For genotype 1b resistance selection, replicon cells are maintained in the presence of asunaprevir at 10 or 30 times the EC50 values (30 or 90 nM final concentrations, respectively)[3]. Asunaprevir, administered at single or multiple doses of 200 to 600 mg twice daily, is generally well tolerated, achieving rapid and substantial decreases in HCV RNA levels in subjects chronically infected with genotype 1 HCV[4].

In Vivo

Asunaprevir (ASV, 3-15 mg/kg, p.o.) displays a hepatotropic disposition (liver-to-plasma ratios ranging from 40- to 359-fold across species) in several animal species. Twenty-four hours postdose, liver exposures across all species tested are ≥110-fold above the inhibitor EC50 observed with HCV genotype-1 replicons[2].

Name

Asunaprevir

CAS

630420-16-5

Formula

C35H46ClN5O9S

Molar Mass

748.29

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Pelosi LA, et al. Effect on HCV Replication by Combinations of Direct Acting Antivirals Including NS5A Inhibitor BMS-790052. Antimicrob Agents Chemother. 2012 Jul 30. [2]. McPhee F, et al. Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032). Antimicrob Agents Chemother. 2012 Aug 6. [3]. McPhee F, et al. Resistance analysis of the hepatitis C virus NS3 protease inhibitor asunaprevir. Antimicrob Agents Chemother. 2012 Jul;56(7):3670-81. [4]. Pasquinelli C, et al. Single- and multiple-ascending-dose studies of the NS3 protease inhibitor asunaprevir in subjects with or without chronic hepatitis C. Antimicrob Agents Chemother. 2012 Apr;56(4):1838-44. [5]. Qi Sun, et al. Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal Transduct Target Ther. 2021 May 29;6(1):212.

PeptideDB

Asunaprevir

CAS: 630420-16-5 F: C35H46ClN5O9S W: 748.29