Canagliflozin

Canagliflozin (JNJ 28431754) is a selective SGLT2 inhibitor with IC₅₀s of 2 nM, 3.7 nM, and 4.4 nM for mSGLT2, rSGLT2, and hSGLT2 in CHOK cells, respectively^[1]. IC50 & Target: IC50: 2/3.7/4.4 nM (mSGLT2/rSGLT2/hSGLT2, in CHOK cells)^[1] 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^[1]. 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^[1].
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^[1].