Grazoprevir-hydrate-MK-5172-hydrate-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGrazoprevir hydrateCat. No.: HY-15298BCAS No.: 1350462-55-3Synonyms: MK-5172 (hydrate)分式: CHNOS分量: 784.92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 mon

2、ths-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (63.70 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.19 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.19 mM); Clear solution1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTI

3、VITY物活性 Grazoprevir hydrate (MK-5172 hydrate)選擇性的丙型肝炎病毒 NS3/4a蛋酶抑制劑，作于gt1b，gt1a，gt2a，gt2b 和 gt3a的 Ki 分別為 0.01 nM，0.01 nM，0.08 nM，0.15 nM 和 0.90 nM。IC50 & Target Ki: 0.01 1體外研究 In biochemical assays, Grazoprevir (MK-5172) is effective against a panel of major genotypes and variantsengineered with com

4、mon resistant mutations, with Ki of 0.01R155K), 0.140.03 nM (gt1bD168V), 0.300.04nM (gt1bD168Y), 5.30.9 nM (gt1bA156T), and 122 nM (gt1bA156V), respectively. In the replicon assay,Grazoprevir demonstrates subnanomolar to low-nanomolar EC50s against genotypes 1a, 1b, and 2a, withEC50s of 0.50.1 nM, 2

5、1 nM, and 21 nM for gt1bcon1, gt1a, and gt2a, respectively. Grazoprevir is potentagainst a panel of HCV replication mutants NS5A (Y93H) (EC50=0.70.3 nM), NS5B nucleosides (S282T)(EC50=0.30.1 nM), and NS5B (C316Y) (EC50=0.40.2) 1. Grazoprevir (MK-5172) maintains the excellentpotency against the gt 3a

6、 enzyme as well as a broad panel of mutant enzymes, has excellent potency in thereplicon system gt1b IC50(50% NHS)=7.4 nM; gt1a IC50(40% NHS)=7 nM, and shows excellent rat liverexposure 2.體內(nèi)研究 Grazoprevir (MK-5172) demonstrates efficacy in vivo against chronic-HCV-infected chimpanzees 1. Whendosed t

7、o dogs, Grazoprevir (MK-5172) shows low clearance of 5 mL/min/kg and a 3 h half-life after iv dosingand has good plasma exposure (AUC=0.4 M h) after a 1 mg/kg oral dose. Dog liver biopsy studies showedthat the liver concentration of Grazoprevir after the 1 mg/kg oral dose is 1.4 M at the 24 h time p

8、oint. Similarto its behavior in rats, Grazoprevir demonstrates effective partitioning into liver tissue and maintains high liverconcentration, relative to potency, 24 h after oral dosing in dogs 2.戶(hù)使本產(chǎn)品發(fā)表的科研獻(xiàn) Nat Methods. 2018 Jul;15(7):519-522. J Gastroenterol. 2019 Jan 25. Antiviral Res. 2017 Mar;

9、139:18-24. Sci Rep. 2019 Apr 5;9(1):5722. J Chromatogr B. 2019 Jan.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Steven Harper , John A. McCauley , Michael T. Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. ACSMed. Chem. Lett., 2012, 3 (4), pp

10、 332-3362. Summa V, Ludmerer SW, McCauley JA, MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity acrossgenotypes and resistant variants. Antimicrob Agents Chemother. 2012 Aug;56(8):4161-7.McePdfHeight2/2 Master of Small Molecules 您邊的抑制劑師www.MedChemECaution: Product has not been fully valid