Emricasan-PF-03491390-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEEmricasanCat. No.: HY-10396CAS No.: 254750-02-2Synonyms: PF 03491390; IDN-6556分式: CHFNO分量: 569.5作靶點: Caspase作通路: Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 42 mg/mL (73.75 mM)

2、* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.7559 mL 8.7796 mL 17.5593 mL5 mM 0.3512 mL 1.7559 mL 3.5119 mL10 mM 0.1756 mL 0.8780 mL 1.7559 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍福渲魄罢埾扰渲瞥吻宓膬湟?，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的

3、作液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.39 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.39 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www

4、.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.39 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Emricasan (PF 03491390)是不可逆的 pan-caspase 抑制劑。IC50 & Target Caspase體內(nèi)研究 Emricasan (IDN-6556) is orally active that is retained in the liver for prolonged period of time. TUNEL-positivecel

5、ls are considerably increased by five-fold in mice fed a HFD and are reduced under Emricasan treatment.In accordance with this observation caspase-3 and -8 are increased in HFD-fed mice by 1.5- and 1.3-foldrespectively and are significantly decreased by Emricasan treatment 1.When comparing efficacy

6、by multipleroutes of administration, Emricasan is administered i.p., p.o., i.m., or i.v. (0.03-3 mg/kg). Caspase 3-likeactivities, measured as DEVD-AMC cleavage, dose dependently decreased with a 92.5% reduction after thehighest dose of Emricasan (3 mg/kg). Emricasan is initially tested in the -Fas

7、model of liver injury, markedhepatocellular apoptosis, and peak ALT activities within 6 h. Emricasan is administered i.p. immediately afteradministration of -Fas, ALT activities, measured 6 h later, decreased in a dose-dependent manner with anED50 value of 0.08 (0.06-0.12) mg/kg 2. Emricasan is a hi

8、ghly selective pan-caspase inhibitordemonstrating irreversible inhibition and a significant first-pass effect. In both syngeneic mouse islets andhuman islets transplanted into immunodeficient mice, Emricasan (i.p., 20 mg/kg) given for 7 days post-transplant led to a significantly enhanced rate of di

9、abetes reversal as compared to vehicle 3.PROTOCOLAnimal Mice 1Administration 12 The male C57BL/6J mice are age-matched and used at approximately 12-16 weeks of age. Four groups arestudied (n=60) with 15 mice per group. Groups 1 and 3 receive regular chow. Groups 2 and 4 receive HFDand 50 g/L (Sucros

10、e) is added to drinking water for 20 weeks. Groups 3 and 4 receive Emricasan 0.3mg/kg/day per os, and Group 1 and 2 receive the vehicle. The oral administration of Emricasan at doses of0.3 mg/kg corresponds to the ED90 value to prevent liver injury in the model of -Fas-induced liver injury.Total bod

11、y weight is measured at 0, 5, 10, 15 and 20 weeks.Rats 2The male Sprague-Dawley rats are cannulated in the carotid artery under isoflurane anesthesia and allowedto recover for at least 1 day before drug administration. Blood (100 L/sample) is taken from the carotidcannula 2 to 240 min after administ

12、ration of Emricasan (i.v., s.c., p.o., or i.p.). Serum is prepared and frozenimmediately until analysis. In studies measuring drug concentrations in portal and systemic blood, individualrats are bled (three animals per time point) simultaneously from the portal vein and inferior vena cava. In thebil

13、iary excretion study, bile is collected from the common bile duct after i.v. and p.o. administration ofEmricasan (10 mg/kg) over a 24-h period on ice and frozen until analysis.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules

14、 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻 Sci Transl Med. 2016 May 18;8(339):339ra69. Nat Protoc. 2015 May;10(5):807-21. J Exp Med. 2018 Jul 2;215(7):1839-1852. Anal Chem. 2017 Sep 19;89(18):9788-9796. Cell Death Dis. 2019 Jun 5;10(6):442.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. B

15、arreyro FJ, et al. The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. Liver Int. 2015 Mar;35(3):953-66.2. Hoglen NC, et al. Characterization of IDN-6556 (3-2-(2-tert-butyl-phenylaminooxalyl)-amino-propionylamino-4-ox

16、o-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid): a liver-targeted caspase inhibitor. J Pharmacol Exp Ther. 2004 May;309(2):634-40.3. McCall M, et al. The caspase inhibitor IDN-6556 (PF3491390) improves marginal mass engraftment after islet transplantation in mice.Surgery. 2011 Jul;150(1):48-55.4. Tian J, et al. Combination of Emricasan with Ponatinib Synergistically Reduces Ischemia/Reperfusion Injury in Rat Brain ThroughSimultaneous Prevention of Apoptosi