Ledipasvir (hydrochloride)

Ledipasvir (GS-5885) hydrochloride is an inhibitor of the hepatitis C virus NS5A, with EC₅₀s of 34 pM and 4 pM against genotype 1a and 1b replicon, respectively. Ledipasvir hydrochloride is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 1.62 μM^[3]. IC50 & Target:EC50: 34 pM (GT1a), 4 pM (GT1b)^[1]
IC50: 1.62 Μm (SARS-CoV 3CLpro)^[3] In Vitro: Ledipasvir hydrochloride has GT1a and 1b EC₅₀ values of 31 and 4 pM, respectively, and protein-adjusted EC₅₀ values of 210 pM (GT1a) and 27 pM (GT1b) and the intrinsic EC₅₀ of 39 is 310 fM for GT1a and 40 fM for GT1b. Ledipasvir hydrochloride is highly protein-bound both in human serum and in the cell-culture medium (containing 10% BSA) of the replicon assay^[1]. Ledipasvir hydrochloride exhibits an EC₅₀ value of 141 nM against the JFH/3a-NS5A replicon^[2]. In Vivo: Ledipasvir hydrochloride is remarkable not only on the basis of its high replicon potency but also on the basis of its low clearance, good bioavailability, and long half-lives in rat, dog, and monkey and low predicted clearance in human. The pharmacokinetics of Ledipasvir hydrochloride is measured in rats and dogs. Ledipasvir shows good half-lives (rat 1.83 hr, dog 2.63 hr) in plasma, low systemic clearance (CL), and moderate volumes of distribution (Vss) that are greater than total body water volume^[1].