Setanaxib-GKT137831-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESetanaxibCat. No.: HY-12298CAS No.: 1218942-37-0Synonyms: GKT137831分式: CHClNO分量: 394.85作靶點: NADPH Oxidase作通路: Metabolic Enzyme/Protease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 : 14.29

2、mg/mL (36.19 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 1.43 mg/mL (3.62 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.43 mg/mL (3.62 mM); Precipitated solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL

3、 ACTIVITY物活性 Setanaxib (GKT137831)是選擇性的NADPH氧化酶 (NOX1/4) 抑制劑，Ki 分別為140和110nM。IC50 & Target Ki: 14040 nM (Nox1), 1750700 nM (Nox2), 11030 nM (Nox4), 410100 nM(Nox5) 1體外研究 Setanaxib (GKT137831) is a potent Nox1/4 inhibitor (Kis=14040/11030 nM) 1. Administration ofSetanaxib (GKT137831) throughout the 7

4、2-hour period of normoxia or hypoxia exposure attenuatesHPASMC proliferation under normoxic conditions at the 20 M concentration but had no effect onproliferation in normoxic HPAECs. In the prevention paradigm, Setanaxib (GKT137831) attenuates hypoxia-induced HPASMC and HPAEC proliferation at 5 and

5、20 M. Complementary assays of cell proliferationmeasuring the expression of PCNA or manual cell counting confirmed that Setanaxib (GKT137831)attenuates hypoxia-induced pulmonary vascular cell proliferation 2.體內研究 During the last half of CCl4 injections, some mice are treated with Setanaxib (GKT13783

6、1) daily. CCl4-induced liver fibrosis is more pronounced in SOD1mu compared to WT mice. Liver fibrosis in both SOD1muand WT mice is attenuated by Setanaxib (GKT137831) treatment. The increased hepatic -SMA expressionis markedly decreased in SOD1mu mice treated with Setanaxib (GKT137831), to a level

7、similar to that of WTmice given the NOX1/4 inhibitor 1.PROTOCOLCell Assay 2 Monolayers of HPAECs and HPASMCs are propagated in culture and placed in normoxic (21% O2, 5%CO2) or hypoxic (1% O2, 5% CO2) conditions for 72 hours. Setanaxib (GKT137831) (0.1-20 M), or vehicle(1% DMSO) are added to the cul

8、ture medium at the onset (prevention regimen) or during the last 24 hours(intervention regimen) of a 72-hour hypoxia exposure regimen 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Specific pathogen-free, wild-type (WT)

9、C57BL/6J mice are used. For the carbon tetrachloride (CCl4) modelof liver fibrosis, 6 week old male mice are injected intraperitoneally with CCl4, which is diluted 1:3 in corn oil,or with vehicle (corn oil) at a dose of 0.5 L/g of body weight twice a week for a total of 12 injections. Duringthe last

10、 half of CCl4 treatment, mice are treated with 60 mg/kg of the NOX1/4 inhibitor Setanaxib(GKT137831) or vehicle by intragastric injection daily. Mice are sacrificed 48 hours after the last CCl4injection. For the bile duct ligation (BDL) model, 6 week old male mice are anesthetized. After laparotomy,

11、the common bile duct is ligated twice and the abdomen closed. The sham operation is performed similarlywithout BDL. From 11 days after operation, mice are treated with 60 mg/kg of the NOX1/4 inhibitor Setanaxib(GKT137831) or vehicle by daily intragastric lavage. Mice are sacrificed 21 days after ope

12、ration. Serumlevels of alanine aminotransferase (ALT) are measured with a commercial kit.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE Antioxid Redox Signal. 2019 May 20;30(15):1831-1848. Bi

13、omed Pharmacother. 2016 Dec 6;86:32-40. Mol Cell Endocrinol. 2016 Dec 5;437:268-279. Arch Biochem Biophys. 2017 Feb 15;616:1-12. Am J Chin Med. 2019 Jul 29:1-19.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Aoyama T, et al. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potentialtherapeutic agent. Hepatology. 2012 Dec;56(6):2316-27.2. Green DE, et al. The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Am J Respir Cell MolBiol. 2012 Nov;47(5):