Background:

Balaglitazone is a partial agonist of peroxisome proliferator-activated receptor (PPAR) γ [1].
PPAR plays important roles in the regulation of insulin, triglycerides and lipid metabolism. It is an attractive target for the therapy of Type II Diabetes. Balaglitazone is a partial agonist of PPARγ. The maximum inhibition of PPARγ activity by balaglitazone is 52%. Thus balaglitazone is supposed to have decreased side effects. It has showed potent effects on lowering blood glucose in various animal models [1 and 2].
In a cell-based assay using HEK293 cells transfected with fused PPARγ, treatment of balaglitazone showed sigmoid activation with an EC50 value of 1.35μM. When combined with rosiglitazone, balaglitazone at increased concentrations resulted in the reduction of rosiglitazone’s activity to the level of balaglitazone alone at concentration of 100 nM [3].
In adult male diabetic mice, the oral administration of balaglitazone at increased doses showed more potent and efficacious at lowering glucose levels than rosiglitazone. Balaglitazone also caused reduction of bodyfluid accumulation andfat accumulation without heart enlargement, indicating that it had a better safety profile on the cardiovascular system. Besides that, balaglitazone treatment lasted for 21 days exerted no significant impact on the volumes of blood or plasma. Moreover, balaglitazone was found to have no effect on bone formation at concentrations of up to 10 mg/kg indicating that it was only a partial agonist and led no loss of bone [1 and 2].
参考文献:
[1] Agrawal R, Jain P, Dikshit SN. Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma (γ) agonist. Mini Rev Med Chem. 2012 Feb;12(2):87-97.
[2] Henriksen K, Byrjalsen I, Nielsen RH, Madsen AN, Larsen LK, Christiansen C, Beck-Nielsen H, Karsdal MA. A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats. Eur J Pharmacol. 2009 Aug 15;616(1-3):340-5.
[3] Larsen PJ, Lykkegaard K, Larsen LK, Fleckner J, Sauerberg P, Wassermann K, Wulff EM. Dissociation of antihyperglycaemic and adverse effects of partial perioxisome proliferator-activated receptor (PPAR-gamma) agonist balaglitazone. Eur J Pharmacol. 2008 Oct 31;596(1-3):173-9.