| In Vitro | In vitro activity: A 922500 inhibits the phylogenetic family members acyl coenzyme A cholesterol acyltransferase-1 and -2 with IC50 of 296 μM. A 922500 potently inhibits huDGAT-1 and mseDGAT-1. |
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| In Vivo | Zucker fatty rats and diet-induced dyslipidemic hamsters are dosed orally with A 922500 (0.03, 0.3, and 3 mg/kg) for 14 days. Serum triglycerides ae significantly reduced by the 3 mg/kg dose of A 922500 in both the Zucker fatty rat (39%) and hyperlipidemic hamster (53%). These serum triglyceride changes are accompanied by significant reductions in free fatty acid levels by 32% in the Zucker fatty rat and 55% in the hyperlipidemic hamster. In addition, high-density lipoprotein-cholesterol is significantly increases (25%) in the Zucker fatty rat by A 922500 administered at 3 mg/kg. A 922500 confers weight loss and a reduction in liver triglycerides when dosed chronically in DIO mice and depletes serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1(-/-) mice. A 922500 (0.03, 0.3 and 3 mg/kg, p.o.) dose-dependently attenuates the maximal postprandial rise in serum triglyceride concentrations. |
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| Animal model | Male Golden Syrian hamsters with hyperlipidemia, and Male Zucker fatty rats |
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| Formulation & Dosage | Dissolved in Polyethylene glycol/hydroxypropyl-β-cyclodextrin (10% w/v); 0.03, 0.3, and 3 mg/kg; oral gavage |
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| References | J Pharmacol Exp Ther. 2009 Aug;330(2):526-31; J Med Chem. 2008 Feb 14;51(3):380-3; Eur J Pharmacol. 2010 Jul 10;637(1-3):155-61. |
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