西咪匹韋作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetSimeprevirCat. No.: HY-10241CAS No.: 923604-59-5分式: CHNOS分量: 749.94作靶點(diǎn): HCV; HCV Protease作通路: Anti-infection; Metabolic Enzyme/Protease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 : 14.29 mg/mL (19.05 mM; Need ultrasonic)SolventMass1 mg 5 mg

2、10 mgConcentration制備儲(chǔ)備液1 mM 1.3334 mL 6.6672 mL 13.3344 mL5 mM 0.2667 mL 1.3334 mL 2.6669 mL10 mM 0.1333 mL 0.6667 mL 1.3334 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?。以下溶解案都?qǐng)先按照 In Vi

3、tro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)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: 1.43 mg/mL (1.91 mM); Clear solution此案可獲得 1.43 mg/mL (1.91 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 14.

4、299999 mg/mL 的澄清DMSO 儲(chǔ)備液加到 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: 1.43 mg/mL (1.91 mM); Clear solution此案可獲得 1.43 mg/mL (1.91 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)。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 14.299999 mg/mL 的澄

5、DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Simeprevir (TMC435) 7.8 nM1。種服有效的 HCV NS3/4A蛋酶抑制劑，Ki 值為 0.36 nM，并抑制HCV 復(fù)制，EC50 值為IC & Target Ki: 0.36 nM (HCV NS3/4A protease)1EC50: 7.8 nM (HCV replication)1體外研究 In Huh7-Luc cells, antiviral activity of simeprevir (TMC435) is dose dependent, and the E

6、C50 and EC90 valuesdetermined for simeprevir (TMC435) are 8 nM and 24 nM, respectively2.simeprevir (TMC435) inhibits NS3/4A proteases from HCV genotypes 1 to 6 with IC50s of 1/0.9/7/30/1.5/2.2/1.6 nMfor 1a/1b/2b/3a/4/5/6, respectively3.體內(nèi)研究 Simeprevir (TMC435) has moderate terminal elimination half-

7、life (t1/2=1.5 h and 4.1 h for rat (3 mg/kg, p.o.), monkey(3 mg/kg, p.o.)3.Animal Model: Sprague-Dawley (SD) rats and cynomolgus monkeys3Dosage: 3 mg/kgAdministration: Oral administrationResult: Time at which peak concentration (Tmax) of 1 hour and 2 hour for rat and monkey,respectively.Concentratio

8、n at 24 h after dosing (C24 h) of 0.9 and 2.3 ng/mL for rat and monkey,respectively.AUC0-24h=1173 and1409 ng h/mL for rat and monkey, respectively.戶(hù)使本產(chǎn)品發(fā)表的科研獻(xiàn) Nat Methods. 2018 Jul;15(7):519-522. 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):

9、867-876. J Med Chem. 2016 Nov 23;59(22):10268-10284. Acta Pharm Sin B. 2019 Jul;9(4):769-781.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Raboisson P, et al. Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors

10、of the hepatitis C virusNS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4853-8.2. Lin TI, et al. In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor.Antimicrob Agents Chemother. 2009Page 2 of 3 www.MedCh

11、emEApr;53(4):1377-85. Epub 2009 Jan 26.3. Rajagopalan R, et al. Preclinical Characterization and Human Microdose Pharmacokinetics of ITMN-8187, a Nonmacrocyclic Inhibitor of the Hepatitis CVirus NS3 Protease. Antimicrob Agents Chemother. 2016 Dec 27;61(1). pii: e01569-16.McePdfHeightCaution: Product has not been fully validated