Canagliflozin | SGLT2 inhibitor

Canagliflozin (842133-18-0) is a potent inhibitor of the sodium-dependent glucose cotransporter 2 (SGLT2), IC₅₀ = 2.2 nM, selective over SGLT1, IC₅₀=910 nM.¹ Dose dependently increases glucose excretion in healthy subjects.² Displays beneficial effects in nonalcoholic fatty liver disease (NAFLD).³ Extends lifespan in male but not female mice.⁴ Inhibits cancer cell proliferation via inhibition of mitochondrial complex-1 supported respiration.⁵ Suppresses the growth of pancreatic cancer cells.⁶

References:

1. Nomura et al. (2010), Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus; J. Med. Chem., 53 6355
2. Shaw et al. (2011), Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects; Diabetes Obes. Metab., 13 669
3. Mantovani et al. (2020), Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials; Metabolites, 11 22
4. Miller et al. (2020), Canagliflozin extends life span in genetically heterogeneous male but not female mice; JCI Insight, 5 e140019
5. Vilani et al. (2016), The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration; Mol. Metab., 5 1048
6. Xu et al. (2020), Inhibitory effects of canagliflozin on pancreatic cancer are mediated via the downregulation of glucose transporter-1 and lactate dehydrogenase A; Int. J. Oncol. 57 1223