- JNJ 24831754ZAE；JNJ 28431754；JNJ 28431754AAA；TA 7284；卡格列净
Canagliflozin是一种高效的，选择性SGLT2抑制剂，作用于hSGLT2，IC50为2.2 nM，比作用于hSGLT1选择性高413倍。Canagliflozin 是新型C-葡萄糖苷，具有噻吩环。Canagliflozin 抑制 Na+依赖性的14C-AMG 吸收，这种作用存在浓度依赖性。Canagliflozin作用于 CHO-hSGLT1 和mSGLT1 细胞，抑制 14C-AMG 吸收，IC50 分别为 0.7 μM 和 >1 μM。
Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.
JNJ 24831754ZAE；JNJ 28431754；JNJ 28431754AAA；TA 7284；卡格列净
DMSO ：82 mg/mL (184.5 mM)
mSGLT2 ,rSGLT2 ,hSGLT2
Canagliflozin is a novel C-glucoside with thiophene ring. Canagliflozin inhibits Na+-dependent 14C-AMG uptake in a concentration-dependent fashion. Canagliflozin inhibits 14C-AMG uptake in CHO-hSGLT1 and mSGLT1 cells with IC50 of 0.7 μM and >1 μM, respectively. Canagliflozin inhibits the facilitative (non-Na+-linked) GLUT-mediated 2H-2-DG uptake in L6 myoblasts by less than 50%. In sham-injected oocytes, Canagliflozin (10 μM) or phlorizin (3 mM) alone in the presence of 50 μM DNJ does not affect currents. In SGLT3-injected oocytes, DMSO and Canagliflozin 10 μM inhibits DNJ-induced currents by 15.6% and 23.4%, respectively.
Canagliflozin shows pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice. Oral administration at 30 mg/kg of Canagliflozin to male SD rats induces glucose excretion over 24 hours by 3,696 mg per 200 g body weight. Pharmacokinetic studies reveals a much higher exposure of Canagliflozin following oral administration. Following intravenous and oral doses of 3 and 10 mg/kg, respectively, to male SD rats, AUC0−inf, po, t1/2 and oral bioavailability are determined to be 35,980 ng·h/mL, 5.2 hours, and 85%, respectively. Thus, inhibition of SGLT2 in renal tubules after oral dosing of Canagliflozin is likely to continuously suppress reabsorption of glucose. The extensive UGE would reflect excellent pharmacokinetic properties of Canagliflozin in vivo as well as high potency of SGLT2 inhibition. Since most of the filtered glucose is reabsorbed by SGLT2 in the renal tubules, the novel compound would be useful for an anti-diabetic agent. Single oral administration of Canagliflozin at 3 mg/kg remarkably reduced blood glucose levels without influencing food intake in hyperglycemic high-fat diet fed KK (HF-KK) mice. There is a 48% reduction in blood glucose level versus vehicle at 6 hours. In contrast, Canagliflozin only slightly affects blood glucose levels in normoglycemic mice. Therefore, Canagliflozin would control hyperglycemia in the therapy of T2DM with low risk of hypoglycemia.