Ledipasvir

Research use only, not for human use.

Ledipasvir is a Hepatitis C Virus NS5A Inhibitor. The mechanism of action of ledipasvir is as a P-Glycoprotein Inhibitor, and Breast Cancer Resistance Protein Inhibitor.

Ledipasvir, also known as GS-5885; is an inhibitor of the hepatitis C virus NS5A protein and is a drug for the treatment of hepatitis C that was developed by Gilead Sciences. On October 10, 2014 the FDA approved the combination product ledipasvir 90 mg/sofosbuvir 400 mg (trade name Harvoni). The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin.

Ledipasvir 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 is highly protein-bound both in human serum and in the cell-culture medium (containing 10% BSA) of the replicon assay. Ledipasvir exhibits an EC50 value of 141 nM against the JFH/3a-NS5A replicon.

Ledipasvir 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 is measured in rats and dogs. Ledipasvir shows good half-lives (rat 1.83 ± 0.22 hr, dog 2.63 ± 0.18 hr) in plasma, low systemic clearance (CL), and moderate volumes of distribution (Vss) that are greater than total body water volume.

GS5885 | GS-5885 | GS 5885 | Ledipasvir

Cell Cycle/DNA Damage

HDAC

GT1a| GT1b

Infection

——

1256388-51-8

889

C49H54F2N8O6

>98% (HPLC)

DMSO : 50 mg/mL. 56.24 mM;H2O : < 0.1 mg/mL

O=C(OC)N[C@H](C(=O)N1[C@H](c2ncc(c3cc4C(F)(F)c5c(ccc(c6ccc7nc([C@H]8N(C(=O)[C@@H](NC(=O)OC)C(C)C)[C@@H]9CC[C@H]8C9)[nH]c7c6)c5)c4cc3)[nH]2)CC2(C1)CC2)C(C)C

Methyl N-[(2S)-1-[(6S)-6-[5-[9,9-Difluoro-7-[2-[(1S,2S,4R)-3-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-3-azabicyclo[2.2.1]heptan-2-yl]-3H-benzimidazol-5-yl]fluoren-2-yl]-1H-imidazol-2-yl]-5-azaspiro[2.4]heptan-5-yl]-3-methyl-1-oxobutan-2-yl]carbamate

(-20℃)

With Ice Pack

≥ 2 years