生物活性

• 靶点

  SGLT2 IC50:4.4nM

  SGLT2 (mouse) IC50:2nM

  SGLT2 (rat) IC50:3.7nM

• 描述Sodium glucose co-transporter 2 (SGLT2) is a high-capacity glucose transporter mediating the majority of the glucose resorption in kidney. Canagliflozin is a selective, potent SGLT2 inhibitor with IC50 values of 4.4, 3.7, and 2.0 nM for human SGLT2, rat SGLT2, and mouse SGLT2, respectively. In contrast, canagliflozin inhibited human, rat and mouse SGLT1 with IC50 values of 684, 571, and >1000 nM, respectively. In L6 myoblasts, canagliflozin at 10 μM blocked the non-Na+-linked GLUT-mediated 3H-2-DG uptake by < 50%. Canagliflozin at 10 μM inhibited DNJ-induced currents by 23.4% in SGLT3-injected oocytes, whereas the same treatment of canagliflozin had no effect on currents in water-injected oocytes. In Zucker diabetic fatty (ZDF) rats treated by 1 mg/kg canagliflozin hemihydrate, renal threshold for glucose excretion was reduced from 415 mg/dl to 94 mg/dl at 90 min post treatment. In db/db mice, single dose of canagliflozin (1 and 10 mg/kg) rapidly downregulated non-fasting blood glucose concentration in a dose-dependent manner at 1h post treatment. When ZDF rats were treated with canagliflozin at different doses (3, 10, or 30 mg/kg) for 4 weeks, the non-fasting blood glucose and the level of HbA1c were decreased in all canagliflozin hemihydrate-treated rats compared to control group. Decreased blood glucose level following an oral glucose tolerance test was also observed in canagliflozin hemihydrate-treated rats. Treatment of 30 mg/kg canagliflozin in DIO mice for 4 weeks decreased their blood glucose level, respiratory exchange ratio, and body weight gain compared to vehicle-treated mice^[2].