Ledipasvir D-tartrate

• CAT Number: I001857
• CAS Number: 1502654-87-6
• Molecular Formula: C53H60F2N8O12
• Molecular Weight: 1039.09
• Purity: ≥95%
• Target: HCV
• Solubility: DMSO: ≥ 28 mg/mL
• Storage: Store at -20C
• IC50: 141 nM (EC50, JFH1/3a-NS5A hybrid replicon) [1]

Ledipasvir (GS5885) D-tartrate is an inhibitor of the hepatitis C virus NS5A protein, which is an experimental drug for the treatment of hepatitis C.IC50 Value: 141 nM (EC50, JFH1/3a-NS5A hybrid replicon) [1]Target: HCVin vitro: Against JFH1/3a-NS5A, DCV was more potent (EC(50) = 0.52 nM) than GS-5885 (EC(50) = 141 nM). DCV sensitivity was increased against JFH1/3a-NS5A-M28V (EC50 = 0.006 nM), A30V (EC(50) = 0.012 nM), and E92A (EC(50) = 0.004 nM) while the NS5A-A30K and -Y93H variants exhibited reduced sensitivity to DCV (EC50 values of 23 nM and 1120 nM, respectively) and to GS-5885 (EC50 values of 1770 nM and 4300 nM, respectively) [1].in vivo: GS-5885 was well tolerated and resulted in median maximal reductions in HCV RNA ranging from 2.3 log(10) IU/ml (1 mg QD) to 3.3 log(10) IU/ml (10 mg QD in genotype 1b and 30 mg QD). E(max) modeling indicated GS-5885 30 mg was associated with>95% of maximal antiviral response to HCV genotype 1a. HCV RNA reductions were generally more sustained among patients with genotype 1b vs. 1a. Three of 60 patients had a reduced response and harbored NS5A-resistant virus at baseline. NS5A sequencing identified residues 30 and 31 in genotype 1a, and 93 in genotype 1b as the predominant sites of mutation following GS-5885 dosing. Plasma pharmacokinetics was consistent with QD dosing [2].

Reference

[1]. Hernandez D, et al. Natural prevalence of NS5A polymorphisms in subjects infected with hepatitis C virus genotype 3 and their effects on the antiviral activity of NS5A inhibitors. J Clin Virol. 2013 May;57(1):13-8.
[2]. Lawitz EJ, et al. A phase 1, randomized, placebo-controlled, 3-day, dose-ranging study of GS-5885, an NS5A inhibitor, in patients with genotype 1 hepatitis C. J Hepatol. 2012 Jul;57(1):24-31.