Velpatasvir

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Chemical Structure| 1377049-84-7 同义名 : GS-5816
CAS号 : 1377049-84-7
货号 : A470907
分子式 : C49H54N8O8
纯度 : 99%
分子量 : 883.0
MDL号 : MFCD28411371
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 5 mg/mL clear

PO 0.5% CMC-Na 31 mg/mL suspension

生物活性
靶点

  • HCV Protease

  • HCV Protease
描述 Chronic hepatitis C virus (HCV) infection afflicts an estimated 71 million individuals worldwide and leads to significant morbidity and mortality, including liver cirrhosis and hepatocellular carcinoma. HCV is comprised of six main genotypes and 86 known subtypes. Further, within these subtypes there are multiple resistance associated substitutions (RAS, plural RASs) in the HCV genome measurable at baseline or appearing during or after treatment[4]. Velpatasvir (VEL, GS-5816) is a novel pan-genotypic hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor with activity against genotype 1 (GT1) to GT6 HCV replicons[5]. The replicon EC50 values (effective concentration to inhibit viral replication by 50%) for velpatasvir, GT(EC50 value): 1a (14 pM); 1b (16 pM); 2a JFH1 (8 pM); 2a J6 (16 pM); 2b (6 pM); 3a (4 pM); 4a (9 pM); 5a (54 pM); 6a (6 pM); 6e (130 pM)[4]. In human liver microsomes, velpatasvir shows no measureable disappearance of parent during a 60 min incubation, leading to a Pred CL < 0.16 L/h/kg. In cryopreserved human he-patocytes 3H-velpatasvir undergoes minimal metabolism and the Pred CL is exceedingly low at 0.06 L/h/kg (4.7% hepatic extraction, Eh%)[4]. The percent free drug in plasma measured by dialysis is similar across species ranging from 0.2 to 0.4% free for rat, dog and cyno; human is within this range at 0.3% free. The steady-state volume of distribution (Vss) is similar across the preclinical species and is larger than total body water ranging from 1.4 to 1.6 L/kg. The half-lives of velpatasvir are 2.3, 5.2 and 5.0h in rat, dog and cyno respectively[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.13mL

0.23mL

0.11mL

5.66mL

1.13mL

0.57mL

11.33mL

2.27mL

1.13mL
参考文献

[1]Lawitz EJ, Dvory-Sobol H, et al. Clinical Resistance to Velpatasvir (GS-5816), a Novel Pan-Genotypic Inhibitor of the Hepatitis C Virus NS5A Protein. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5368-78.

[2]Jackson WE, Everson GT. Sofosbuvir and velpatasvir for the treatment of hepatitis C. Expert Rev Gastroenterol Hepatol. 2017 Jun;11(6):501-505.

[3]EPCLUSA

[4]Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK. Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®. Bioorg Med Chem Lett. 2019 Aug 15;29(16):2415-2427. doi: 10.1016/j.bmcl.2019.04.027. Epub 2019 May 4. PMID: 31230974.

[5]Lawitz EJ, Dvory-Sobol H, Doehle BP, Worth AS, McNally J, Brainard DM, Link JO, Miller MD, Mo H. Clinical Resistance to Velpatasvir (GS-5816), a Novel Pan-Genotypic Inhibitor of the Hepatitis C Virus NS5A Protein. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5368-78. doi: 10.1128/AAC.00763-16. PMID: 27353271; PMCID: PMC4997818.