Orlistat
Orlistat is a digestive lipase inhibitor.{60573,16688,60574} It inhibits diacylglycerol lipase ? (DAGL?), DAGL?, ?/?-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.{14179} It also inhibits fatty acid synthase (FASN; apparent Ki = ~0.1 µM for the human enzyme) and the proliferation of PC3 prostate cancer cells in a concentration-dependent manner.{60575} Orlistat (10 mg/kg) decreases serum cholesterol levels and total body weight in a mouse model of obesity induced by a high-fat diet.{60576} Formulations containing orlistat have been used in the treatment of adult obesity.
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