product name Ledipasvir (GS5885)
Description: Ledipasvir (also known as GS5885) is a HCV NS5A polymerase inhibitor and is used for the treatment of hepatitis C virus infection. FDA approved the combination product of ledipasvir 90 mg/sofosbuvir 400 mg (trade name Harvoni) in October 2014. 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.
References: J Med Chem. 2014 Mar 13;57(5):2033-46.
889.0
Formula
C49H54F2N8O6
CAS No.
1256388-51-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (112.5 mM)
Water: <1 mg/mL
Ethanol: 100 mg/mL (112.5 mM)
Solubility (In vivo)
Synonyms
GS-5885
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19424216
| In Vitro |
In vitro activity: Ledipasvir is a specific inhibitor of HCV NS5A protein to inhibit HCV replication in the HCV subgenomic replicon system. NS5A replication complex inhibitors are novel antiviral factors for HCV treatment. Typically, these inhibitors have high efficiency and low viral resistance when compared to traditional HCV replication inhibitor targeted on NS3 helicase and NS5B RNA polymerasae. NS5A inhibitors are supposed to bind across the NS5A dimer interface, proximal to N-terminal domain 1. The binding is thought to distort dimer association directly or allosterically, which may disrupt NS5A function in HCV RNA replication. When a JFH1/3a-NS5A hybrid replicon was used to assess susceptibility to NS5A, another inhibitor DCV was shown to be more potent than ledipasvir. Additionally, NS5A-A30K and -Y93H variants exhibited reduced sensitivity to ledpasvir (EC50 value of 1770 nM and 4300 nM respectively). Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In clinical trials, it was observed ledpasvir was well tolerated and exhibited median maximal reduction of HCV RNA ranging from 2.3 log10 IU/ml to 3.3 log10 IU/ml. Emax modeling also showed administration of 30 mg ledpasvir after 3 days resulted in >95% maximal response of HCV RNA reduction to genotype 1a.Finally, it was also observed that HCV RNA was more sustained in genotype 1b compared to 1a. |
| Animal model | |
| Formulation & Dosage | |
| References | J Clin Virol. 2013 May;57(1):13-8; J Hepatol. 2012 Jul;57(1):24-31; Nature. 2010 May 6;465(7294):96-100. |
