Cell lines

HepG2 hepatoma cells

Preparation method

The solubility of this compound in DMSO is > 21.25 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1 μM, 60 min

Applications

In HepG2 cell lysates, A-922500 (1 μM) inhibited about 99% of recombinant DGAT1 enzymatic activity. Exposure of HepG2 cells to A-922500 dose-dependently inhibited TG synthesis (stable isotope-labeled triolein; 13C18-oleoyl, 13C18-oleoyl, 13C18-oleoyl). In HEK293 cells expressing DGAT1, A-922500 inhibited [13C18]oleoyl triolein incorporation with the IC50 values of 17 nM.

Animal models

Zucker fatty rats and diet-induced dyslipidemic hamsters, DIO mice, DGAT-1(-/-) mice,

Dosage form

oral gavage

Application

In Zucker fatty rats and diet-induced dyslipidemic hamsters, oral administration of A 922500 (3 mg/kg, 14 days) significantly reduced serum triglycerides and free fatty acid levels. A 922500 (3 mg/kg) significantly increased high-density lipoprotein-cholesterol. In DIO mice, A 922500 induced weight loss and reduced liver triglycerides when dosed chronically. A 922500 depleted 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 attenuated the maximal postprandial rise in serum triglyceride concentrations.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

A922500 is a potent, active, selective and orally bioavailable inhibitor of diacylglycerol acyltransferase-1 (DGAT-1). It is a small molecular with the formula of C₂₆H₂₄N₂O₄and molecular weight of 428.48. A922500 inhibits human DGAT-1 with an IC50 value of 9 nM, but does not inhibit other acyltransferases, such as DGAT-2, ACAT-1 and ACAT-2.^[1]Diacylglycerol acyltransferase (DGAT) catalyzes esterification of 1,2-diacylglycerol (DAG) with fatty acyl-CoA to form triglycerides (TG) at the endoplasmic reticulum.^[2]

Reference

[1] Andrew J. K, Jason A. S, Kelly J. L, Andrew J. S, Philip R. K, Regina M. R, et al. In vivo efficacy of acyl CoA: Diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia. European Journal of Pharmacology. 2010, 637. 155-161.

[2] Kyeong L, Ja-Il G, Hwa Young J, Minkyoung K, Shanthaveerappa K. B, et al. Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors. Bioorganic & Medicinal Chemistry Letters. 2012, 22. 7456–7460.