Orlistat-d₃is intended for use as an internal standard for the quantification of orlistat by GC- or LC-MS. Orlistat is a digestive lipase inhibitor.^1,2,3It inhibits diacylglycerol lipase α (DAGLα), DAGLβ, α/β-hydrolase domain-containing protein 12 (ABHD12), ABHD16A, and platelet-activating factor acetylhydrolase (PAF-AH; IC₅₀s = 0.06, 0.1, 0.08, 0.03, and 0.05 µM, respectively), as well as pancreatic lipase and hormone-sensitive lipase (IC₅₀s = 0.65 and 2.1 µg/ml, respectively) but does not inhibit fatty acid amide hydrolase (FAAH) or KIAA1363 (IC₅₀s = >100 µM for both). Orlistat decreases ionomycin-induced production of the endocannabinoid 2-arachidonoyl glycerol (2-AG) in N18TG2 murine neuroblastoma cells when used at a concentration of 1 µM.⁴It also inhibits fatty acid synthase (FASN; K_iapp= ~0.1 µM for the human enzyme) and the proliferation of PC3 prostate cancer cells in a concentration-dependent manner.⁵Orlistat (10 mg/kg) decreases serum cholesterol levels and total body weight in a mouse model of obesity induced by a high-fat diet.⁶Formulations containing orlistat have been used in the treatment of adult obesity.

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