Ledipasvir-GS-5885-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELedipasvirCat. No.: HY-15602CAS No.: 1256388-51-8Synonyms: GS-5885分式: CHFNO分量: 889作靶点: HCV; HCV Protease作通路: Anti-infection; Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实

2、验 DMSO : 50 mg/mL (56.24 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (2.81 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (2.81 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Ledipasvir种有效的

3、HCV NS5A 抑制剂，能够抑制 GT1a 和 GT1b 复制，EC50 值分别为 34 pM 和 4pM。IC50 & Target EC50: 34 pM (GT1a), 4 pM (GT1b) 1体外研究 Ledipasvir has GT1a and 1b EC50 values of 31 and 4 pM, respectively, and protein-adjusted EC50 values of210 pM (GT1a) and 27 pM (GT1b) and the intrinsic EC50 of 39 is 310 fM for GT1a and 40 fM

4、for GT1b.Ledipasvir is highly protein-bound both in human serum and in the cell-culture medium (containing 10% BSA)of the replicon assay 1. Ledipasvir exhibits an EC50 value of 141 nM against the JFH/3a-NS5A replicon 2.体内研究 Ledipasvir is remarkable not only on the basis of its high replicon potency

5、but also on the basis of its lowclearance, good bioavailability, and long half-lives in rat, dog, and monkey and low predicted clearance inhuman. 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 syste

6、mic clearance (CL), and moderate volumes ofdistribution (Vss) that are greater than total body water volume 1.PROTOCOLAnimal Rats, Dogs and Monkeys 1Administration 1 Pharmacokinetic studies are performed in male nave Sprague-Dawley(SD) rats, non-naive beagle dogs, andcynomolgus monkeys (three animal

7、s per dosing route). Intravenous (IV) administration is dosed via infusionover 30 min in a vehicle containing 5% ethanol, 20% PEG400, and 75% water (pH adjusted to 3.0 with HCl).Oral dosing is administered by gavage in a vehicle containing 5% ethanol, 45% PEG 400, and 50% of 50 mMcitrate buffer, pH

8、3. Blood samples are collected over a 24 h period postdose into Vacutainer tubescontaining EDTA-K2. Plasma was isolated, and the concentration of the test compound in plasma wasdetermined with LC/MS/MS after protein precipitation with acetonitrile.MCE has not independently confirmed the accuracy of

9、these methods. They are for reference only.户使本产品发表的科研献 Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):1922-1927. Int J Radiat Oncol Biol Phys. 2016 Nov 15;96(4):867-876. J Gastroenterol. 2019 Jan 25. Antimicrob Agents Chemother. 2015 Jun;59(6):3482-92. Antimicrob Agents Chemother. 2015 May;59(5):2496-

10、507.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE1. Link JO, et al. Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection.J Med Chem. 2014 Mar 13;57(5):2033-462. Hernandez D, et al. Natural prevalence of NS5A polymorphisms in subjects infected with hepatitis C virus genotype 3 and their effectson the antiviral activity of NS5A inhibitors. J Clin Virol. 2013 May;57(1):13-8.McePdfHeightCaution: Product has not been