雷迪帕韦作用机制 - Medchemexpress - MCE中国

1、Product Data SheetLedipasvirCat. No.: HY-15602CAS No.: 1256388-51-8分式: CHFNO分量: 889作靶点: HCV作通路: Anti-infection储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (56.24 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制

2、备储备液1 mM 1.1249 mL 5.6243 mL 11.2486 mL5 mM 0.2250 mL 1.1249 mL 2.2497 mL10 mM 0.1125 mL 0.5624 mL 1.1249 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加

3、助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (2.81 mM); Clear solution此案可获得 2.5 mg/mL (2.81 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到

4、 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (2.81 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (2.81 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICA

5、L ACTIVITY物活性 Ledipasvir种有效的 HCV NS5A 抑制剂，能够抑制 GT1a 和 GT1b 复制，EC50 值分别为 34 pM 和 4 pM。IC & 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 of 210 pM(GT1a) and 27 pM (GT1b) and the intrinsic EC50 of 39 is

6、 310 fM for GT1a and 40 fM for GT1b. Ledipasvir is highlyprotein-bound both in human serum and in the cell-culture medium (containing 10% BSA) of the replicon assay1.Ledipasvir exhibits an EC50 value of 141 nM against the JFH/3a-NS5A replicon2.体内研究 Ledipasvir is remarkable not only on the basis of i

7、ts 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. Thepharmacokinetics of Ledipasvir is measured in rats and dogs. Ledipasvir shows good half-lives (rat 1.83 0.22 hr, dog2.63 0.18

8、 hr) in plasma, low systemic clearance (CL), and moderate volumes of distribution (Vss) that are greaterthan total body water volume1.PROTOCOLAnimal Rats, Dogs and Monkeys1Administration 1 Pharmacokinetic studies are performed in male nave Sprague-Dawley(SD) rats, non-naive beagle dogs, andcynomolgu

9、s monkeys (three animals per dosing route). Intravenous (IV) administration is dosed via infusion over 30min in a vehicle containing 5% ethanol, 20% PEG400, and 75% water (pH adjusted to 3.0 with HCl). Oral dosing isadministered by gavage in a vehicle containing 5% ethanol, 45% PEG 400, and 50% of 5

10、0 mM citrate buffer, pH 3.Blood samples are collected over a 24 h period postdose into Vacutainer tubes containing EDTA-K2. Plasma wasisolated, and the concentration of the test compound in plasma was determined with LC/MS/MS after proteinprecipitation with acetonitrile.MCE has not independently con

11、firmed the accuracy of 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 May;54(5):449-458. Antimicrob Agents Chemother. 2015 Jun;59(6):3482-92. Antimicrob Agen

12、ts Chemother. 2015 May;59(5):2496-507.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCESPage 2 of 3 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 effects on the antiviralactivity of NS5A inhibitors. J Clin Virol. 2013 May;57(1):13-8.McePdfHeightCaution: Product h