雷迪帕韋作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetLedipasvirCat. No.: HY-15602CAS No.: 1256388-51-8分式: CHFNO分量: 889作靶點(diǎn): HCV作通路: Anti-infection儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (56.24 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制

2、備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加

3、助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (2.81 mM); Clear solution此案可獲得 2.5 mg/mL (2.81 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到

4、 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (2.81 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (2.81 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICA

5、L ACTIVITY物活性 Ledipasvir種有效的 HCV NS5A 抑制劑，能夠抑制 GT1a 和 GT1b 復(fù)制，EC50 值分別為 34 pM 和 4 pM。IC & Target EC50: 34 pM (GT1a), 4 pM (GT1b)1體外研究 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.體內(nèi)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.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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