Indeglitazar-PPM-204-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEIndeglitazarCat. No.: HY-14817CAS No.: 835619-41-5Synonyms: PPM 204分式: CHNOS分量: 389.42作靶點(diǎn): PPAR作通路: Cell Cycle/DNA Damage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 : 33 mg/mL (84.74 mM;

2、Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.5679 mL 12.8396 mL 25.6792 mL5 mM 0.5136 mL 2.5679 mL 5.1358 mL10 mM 0.2568 mL 1.2840 mL 2.5679 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，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Indeglitazar種具有服活性的 PPAR 泛激動(dòng)劑，對(duì) PPAR 亞型 alpha ()，delta () 和 gamma

3、()都有作活性。IC50 & Target PPAR PPAR PPAR體外研究In an assay of preadipocyte differentiation, measuring in part functional insulin sensitization capability of the1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEcells, Indeglitazar shows an EC50 of 0.32 M compared with Rosiglitazone, which shows an EC50 of 13

4、 nM,although the maximal response obtained from the 2 compounds is comparable 1.體內(nèi)研究 An initial assessment of in vivo activity is carried out using the Zucker rat model of diabetes. The significantlowering of glucose, HbA1C, triglycerides, and total cholesterol are observed after i.v. treatment with

5、 10mg/kg Indeglitazar once per day for 3 weeks. Notably, the level of Adiponectin (on day 21) is essentiallyunchanged in treated vs. untreated animals (4.8 mcg/mL vs. 4.9 mcg/mL), thus the observed reductions inglucose and HbA1C are achieved in an adiponectin-independent fashion. These differences i

6、n the effects ofIndeglitazar in vivo may be a consequence of synergy between the 3 PPAR activities or because of theSPPARM profile of the compound, or a combination of these factors. The oral activity of Indeglitazar isassessed in the ob/ob model of diabetes and insulin resistance. Indeglitazar sign

7、ificantly decreases glucose,insulin, triglycerides, and free fatty acid levels 1.PROTOCOLKinase Assay 1 The purified PPAR_ LBD protein is diluted to 12 mg/mL and 1mM of Indeglitazar and 2x molar excess ofsteroid receptor coactivator-1 (SRC-1) peptide are added before crystallization by mixing equal

8、volumes of aprotein/compound sample with reservoir solution containing 27% polyethylene glycol (PEG) 4000, 0.1 M 2-(bis-(2-hydroxy-ethyl)-amino)-2-hydroxymethyl- propane-1,3-diol (BisTris) buffer at pH 6.5, 0.2 M ammoniumacetate, and 5% glycerol. The crystals are soaked in cryo-protective buffer (30

9、% PEG 4000, 0.1 M BisTrisbuffer at pH 6.5, 0.2 M ammonium acetate, and 5% glycerol) before flash-freezing in liquid nitrogen for datacollection 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 1Administration 1 Indeglitazar is administered

10、once daily i.v. as a solution (10% SolutolHS15,10%ethanol,80%saline) toZDF/GmiCrl-fa/fa rats. Treatment is initiated at age 7-8 weeks, and blood samples are analyzed before thetreatment and 21 days after the treatment.Mice 1Ob/ob mouse study. Indeglitazar (10 mg/kg) or Pioglitazone (30 mg/kg) are or

11、ally administered to 9-week-oldB6.V-Lepob mice for 14 days. Compounds are suspected in 0.5% methylcellulose and 2% Tween 80 beforedosing. On the last day, blood is collected for insulin, triglyceride, free fatty acid, and adiponectinmeasurements.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Artis DR, et al. Scaffold-based discovery of Indeglitazar, a PPAR pan-active anti-diabetic agent. Proc Natl Acad Sci U S A. 2009 Jan6;106(1):262-7.McePdfHeightCaution: Produc