Gemfibrozil-CI-719-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGemfibrozilCat. No.: HY-B0258CAS No.: 25812-30-0Synonyms: CI-719分式: CHO分量: 250.33作靶点: PPAR; Cytochrome P450作通路: Cell Cycle/DNA Damage; Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 mon

2、th溶解性数据体外实验 DMSO : 34 mg/mL (135.82 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 3.9947 mL 19.9736 mL 39.9473 mL5 mM 0.7989 mL 3.9947 mL 7.9895 mL10 mM 0.3995 mL 1.9974 mL 3.9947 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Gem

3、fibrozil种 PPAR- 激活剂，为种降脂药；Gemfibrozil 同时 P450 的选择性抑制剂，对CYP2C9，2C19，2C8 和 1A2 的 Ki 值分别为 5.8，24，69 和 82 M。IC50 & Target PPAR- CYP2C9 CYP2C19 CYP2C85.8 M (Ki) 24 M (Ki) 69 M (Ki)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemECYP1A282 M (Ki)体外研究 Gemfibrozil is an activator of PPAR-, used as a lipid-lo

4、wering drug 1; also a nonselective inhibitor ofseveral P450 isoforms, with Ki values for CYP2C9, 2C19, 2C8, and 1A2 of 5.8, 24, 69, and 82 M,respectively 3. Gemfibrozil (100, 150, 200 M) inhibits the cytokine-induced NO production in aconcentration dependent manner in human U373MG astroglial cells,

5、and such effects are not due to anychange of the stability of iNOS mRNA. Gemfibrozil (50, 100, 200 M) inhibits human iNOS promoter-derivedluciferase activity in cytokine-stimulated human U373MG astroglial cells. Furthermore, Gemfibrozil (50, 100,150, and 200 M) shows no effects on the viability of t

6、he cells 1. Gemfibrozil considerably inhibits both M-23and M-1 formation (catalyzed by CYP2C8 and CYP3A4), with Ki (IC50) values of 69 M (95 M) and 273 M(250 M), respectively, in human liver microsomes. Gemfibrozil (0-250 M) dose dependently inhibits theformation of M-23 (IC50, 68 M) and M-1 (IC50,

7、78 M) in recombinant CYP2C8, but shows no appreciableeffect on the formation of these metabolites in recombinant CYP3A4 3.体内研究 Gemfibrozil (62 mg/kg/day, p.o.) treatment initiated 3 days before spinal cord injury (SCI) causes decreasedlocomotor function, and induces a trend for decreased white matte

8、r sparing after injury in mice. Gemfibrozil(62 mg/kg/day, p.o.) decreases macrophage immunoreactivity but increases T cell infiltration into sparedtissue 2.PROTOCOLKinase Assay 3 Activities of CYP3A4 (testosterone 6-hydroxylation) and CYP2C8 (paclitaxel 6-hydroxylation) aredetermined. The marker sub

9、strate concentrations used, 25 M testosterone and 1 to 5 M paclitaxel, arecomparable with or around the Km values of the reactions. Gemfibrozil is either coincubated at 37C for 15min with the marker substrate and NADPH (1 mM) before the reaction is initiated with human livermicrosomes (0.1 mg/mL) or

10、 preincubated with human liver microsomes and NADPH for 15 min before addingthe marker substrate 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Briefly, 400 L of culture supernatant is allowed to react with 200 L of Griess reagent and in

11、cubated at roomtemperature for 15 min. The optical density of the assay samples is measured spectrophotometrically at 570nm. Fresh culture medium serves as the blank in all experiments. Nitrite concentrations are calculated from astandard curve derived from the reaction of NaNO2 in the assay 1.MCE h

12、as not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice are given vehicle or gemfibrozil beginning 3 days before SCI to ensure drug availability at the time ofAdministration 2 the injury (n=5-6/group). The drug is delivered orally by dissolving it in eth

13、anol (0.25% w/w of gemfibrozil) andcoating food pellets such that each animal receives appr 62 mg/kg/day; chow for control groups is treatedwith ethanol. Ethanol for each group is allowed to completely evaporate before giving the food to the animals.In addition, animals receive an intraperitoneal in

14、jection of vehicle or gemfibrozil (500 g dissolved in 200 LPBS) 1 h after the injury, and then continued to receive the drug in their food until the end of the study (28days post-injury) 2.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these meth

15、ods. They are for reference only.户使本产品发表的科研献 Chemosphere. 2019 Mar.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Pahan K, et al. Gemfibrozil, a lipid-lowering drug, inhibits the induction of nitric-oxide synthase in human astrocytes. J Biol Chem. 2002Nov 29;277(48):45984-91. Epub 2002 Sep 18.2. Almad A, et al. The PPAR alpha agonist gemfibrozil is an ineffective treatment for spinal cord injured mice. Exp Neurol. 2011Dec;232(2):309-17.3. Wang JS, et al. Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. Dr