Canagliflozin

A highly potent and selective SGLT2 inhibitor with IC50 of 4.4, 3.7 and 2.0 nM for hSGLT2, rSGLT2 and mSGLT2, respectively; displays >100-fold selectivity over SGLT1; improves glycemic control and beta-cell function in rodent models of T2DM, and reduces body weight gain in rodent models of obesity.Diabetes Approved (In Vitro) :Canagliflozin inhibits Na+-dependent 14C-AMG uptake in CHO-hSGLT2 cells, with an IC50 of 4.4±1.2 nM. Similar IC50 values are obtained in CHO-rSGLT2 and CHO-mSGLT2 cells (IC50 = 3.7 and 2.0 nM for rat and mouse SGLT2, respectively) . Canagliflozin inhibits 14C-AMG uptake in CHO-hSGLT1 and mSGLT1 cells with IC50 of 684±159 nM and >1,000 nM, respectively. (In Vivo) :Canagliflozin (30 mg/kg treatment for 4 weeks) reduces blood glucose (BG) levels, respiratory exchange ratio, and body weight gain in DIO mice.Canagliflozin (3 mg/kg for 3 weeks) increases urinary glucose excretion (UGE) with no significant change in total food intake compared with that in vehicle-treated rats, leading to a decrease in body weight In ZF rats.