Atglistatin - ATGL 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAtglistatinCat. No.: HY-15859CAS No.: 1469924-27-3分式: CHNO分量: 283.37作靶点: ATGL作通路: Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (352.90 mM)H2O : 40% PEG

2、300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (8.82 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (8.82 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Atglistatin种选择性的脂 油三酯脂酶 (ATGL) 抑制剂，体外抑制脂解作，IC50 为 0.7 M。IC50 & Target IC5

3、0: 0.7 M (ATGL) 1体外研究 Atglistatin inhibits Triacylglycerol (TG) hydrolase activity of wild-type white adipose tissue (WAT) in a dose-dependent manner up to 78% at the highest concentration. In comparison to wild-type preparations, TGhydrolase activity in WAT lysates from ATGL-ko animals is reduced b

4、y approximately 70% and Atglistatinhad only a moderate effect on the residual activity. The combined use of Atglistatin and the hormone-sensitive lipase (HSL) inhibitor Hi 76-0079 leads to an almost complete inhibition (-95%) of TG hydrolaseactivity of WAT which implicates that most of the non-ATGL

5、activity can be ascribed to HSL 1.体内研究 Animals receive Atglistatin dissolved in olive oil by oral gavage. After application, blood and tissues arecollected for determination of plasma parameters, tissue Triacylglycerol (TG) levels, and inhibitorconcentrations. Time-course experiments revealed that t

6、he lipolytic parameters fatty acids (FA) and glycerolare reduced 4 and 8 hours after application and returned to normal after 12 hours. Eight hours aftertreatment, a dose-dependent decrease is observed in FA and glycerol levels up to 50% and 62%,respectively. Atglistatin also caused a strong reducti

7、on in plasma TG levels (-43%) while blood glucose, totalcholesterol, ketone bodies, and insulin levels do not significantly change. Dose and time-dependent inhibitionof lipolysis is also observed in response to intraperitoneal injection of Atglistatin 1.PROTOCOLCell Assay 1 For MTT-based in vitro vi

8、ability assays, cells are seeded at an initial density of 1104 cells per well in 96-wellplates and cultured under standard conditions for 24 hours. The next day, cells are pretreated with differentconcentrations of Atglistatin dissolved in DMSO or Cisplatin dissolved in dimethylformamide (DMF) aspos

9、itive control for two hours. Medium is replaced by an identical fresh medium and incubated again for theindicated time-points. Thereafter cells are incubated for 3 hours with 100 L Thiazolyl Blue TetrazoliumBromide (MTT). The resulting violet formazan crystals are dissolved by adding 100 L of MTT so

10、lubilizationsolution (0.1% NP-40, 4 mM HCl and anhydrous isopropanol). After complete dissolution of the formazanproduct, absorbance is measured at 595 nm using 690 nm as reference wavelength 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice

11、 1Administration 1 Mice (C57Bl/6J) are used. Atglistatin is administrated orally by gavage in olive oil (200 L) or by IP injection.For IP administration, we generated Atglistatin hydrochloride by the addition of 25 % HCl resulting in a watersoluble compound. For intraperitoneal injection the inhibit

12、or is dried, excess HCl is buffered with Tris base,and Atglistatin is dissolved in PBS containing 0.25 % Cremophor EL (pH 7.1). Atglistatin is administeredorally by gavage in olive oil (1.4 mg/mouse). After 8 h tissues are collected and extracted twice using Folchprocedure. Combined organic phases a

13、re concentrated, reconstituted in 500 L chloroform and ssubjected tosolid phase extraction (SPE). For SPE samples are loaded onto silica columns washed twice with 2 mL of2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEchloroform and Atglistatin is eluted using 3 mL chloroform/methanol (99/1, v/v).

14、Eluted samples areconcentrated, dissolved in n-propanol/chloroform/methanol (8/1.3/0.6, v/v/v) and analyzed by UPLC/MS (m/z284, MH+; SYNAPT G1 qTOF HD mass spectrometer, Waters).MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Fish Physiol Biochem. 2017 Jun;43(3):813-822.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Mayer N, et al. Development of small-molecule inhibitors targeting adipose triglyceride lipase. (2013) Nat Che