Atglistatin

Atglistatin is a highly potent, selective and competitive inhibitor of adipose triglyceride lipase (ATGL) with an IC50 of ~0.7 μM for inhibition of lipolysis in vitro, but no toxicity up to a concentration of 50 μM. (In Vitro) :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, TG hydrolase activity in WAT lysates from ATGL-ko animals is reduced by approximately 70% and Atglistatin had 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 hydrolase activity of WAT which implicates that most of the non-ATGL activity can be ascribed to HSL. (In Vivo) :Animals receive Atglistatin dissolved in olive oil by oral gavage. After application, blood and tissues are collected for determination of plasma parameters, tissue Triacylglycerol (TG) levels, and inhibitor concentrations. Time-course experiments revealed that the lipolytic parameters fatty acids (FA) and glycerol are reduced 4 and 8 hours after application and returned to normal after 12 hours. Eight hours after treatment, a dose-dependent decrease is observed in FA and glycerol levels up to 50% and 62%, respectively. Atglistatin also caused a strong reduction in plasma TG levels (-43%) while blood glucose, total cholesterol, ketone bodies, and insulin levels do not significantly change. Dose and time-dependent inhibition of lipolysis is also observed in response to intraperitoneal injection of Atglistatin.

1469924-27-3

Atglistatin

>98% (HPLC)

Ethanol: 4 mg/mL (14.11 mM) ; DMSO: 57 mg/mL (201.15 mM)

CN (C1=CC=C (C=C1) C2=CC (NC (N (C) C) =O) =CC=C2) C

C17H21N3O

283.37

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.