Animal models

ob/ob mice

Dosage form

10 mg/kg; b.i.d.

Applications

In ob/ob mice, A939572 lowered the desaturation index (18:0/18:1n9). Moreover, A939572 reduced triglyceride desaturation index in a dose-dependent manner.

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.

A939572 is a potent and orally bioavailable inhibitor of stearoyl-CoA desaturase1 (SCD1) with IC50 value of 37nM [1].

SCD is a microsomal enzyme that catalyzes the biosynthesis of monounsaturated fatty acids. One member of SCD family, SCD1, is regulated by dietary and hormonal factors and is proved to play an important role in lipid metabolism and body weight control. Thus, SCD1 is a target for the treatment of obesity and diabetes. A939572 is a synthetic inhibitor of SCD1 with improved inhibitory activity and lipophilicity than its parent compound. It shows inhibition of mouse SCD1 and human SCD1 with IC50 values of<4nM and 37nM, respectively. In addition, A939572 has no inhibitory activity to the co-enzymes of SCD1, cytochrome b5 and cytochrome b5 reductase. It suggests that A939572 interacts with SCD1 directly and specifically. Furthermore, A939572 shows high oral bioavailability in mice [1].

References:
[1] Xin Z, Zhao H, Serby M D, et al. Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors. Bioorganic & medicinal chemistry letters, 2008, 18(15): 4298-4302.