A 922500 (DGAT-1 Inhibitor 4a) is a potent, selective, and orally bioavailable diacylglycerol acyltransferase 1 (DGAT-1) inhibitor with IC₅₀s of 9 and 22 nM against human and mouse DGAT-1, respectively.

IC50: 9 nM (human DGAT-1), 22 nM (mouse DGAT-1)^[1]

A 922500 (A-922500) demonstrates excellent selectivity over other acyltransferases, including DGAT-2 (IC₅₀=53 μM) and the phylogenetic family members acyl coenzyme A cholesterol acyltransferase-1 and -2 (IC₅₀=296 μM) ^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

DGAT-1 inhibitor A 922500 (A-922500) reduces serum triglyceride levels from baseline at all doses tested; however, this is only statistically significant at the 3 mg/kg dose, which lowers serum triglycerides by 53%. Similarly, the 3 mg/kg dose of A 922500 significantly reduces serum FFA concentrations by 55% and total cholesterol by 25%. DGAT-1 inhibition has no significant effect on body weight at any dose tested. Although A 922500 dpes not significantly affect LDL-cholesterol or HDL-cholesterol individually, the serum LDL/HDL-cholesterol ratio is significantly improved by A 922500 at 0.3 and 3 mg/kg. Similar to the dyslipidemic hamster, treatment with 3 mg/kg A 922500 significantly reduces serum triglyceride concentrations (39%). FFA levels significantly increase over the 14-day period in vehicle-treated animals. This increase is inhibited in a dose-dependent manner by A 922500 such that FFA concentrations are 32% lower after 14 days of treatment with the DGAT-1 inhibitor at 3 mg/kg, compared with the vehicle group (p < 0.05). HDL-cholesterol is significantly increased from baseline levels by A 922500 at 0.3 and 3 mg/kg; however, this is only significantly increased compared with vehicle at the 3 mg/kg dose. Body weight significantly increases over the 2-week period in vehicle-treated rats, and this is not affected by A 922500. LDL-cholesterol is significantly reduced in the vehicle treated group. DGAT-1 inhibition does not further reduce LDL-cholesterol and has no effect on total cholesterol^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

428.48

C₂₆H₂₄N₂O₄

959122-11-3

Solid

Off-white to yellow

O=C(NC1=CC=C(C2=CC=C(C([C@@H]3CCC[C@H]3C(O)=O)=O)C=C2)C=C1)NC4=CC=CC=C4

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. King AJ, et al. Diacylglycerol acyltransferase 1 inhibition lowers serum triglycerides in the Zucker fatty rat and the hyperlipidemic hamster. J Pharmacol Exp Ther. 2009 Aug;330(2):526-31.  [Content Brief]