**Background**
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia, which can lead to severe complications including nephropathy, neuropathy, and cardiovascular disease. A key mechanism in the regulation of blood glucose is the reabsorption of glucose in the proximal tubules of the kidney, a process primarily mediated by the sodium/glucose cotransporter 2 (SGLT2). By inhibiting SGLT2, glucose excretion can be increased via the urine, thereby lowering blood glucose levels independently of insulin. Beyond glycemic control, SGLT2 inhibition has shown potential in reducing oxidative stress and inflammation in renal tubular cells, which are often damaged by glucose overload. In this context, we will introduce a potent and highly specific SGLT2 inhibitor – Tofogliflozin.
**Definition**
Tofogliflozin is a highly selective SGLT2 inhibitor with an IC50 of 2.9 nM. According to the Tofogliflozin description, it exhibits Ki values of 2.9 nM, 14.9 nM, and 6.4 nM for human, rat, and mouse SGLT2, respectively.
**In Vitro and In Vivo Studies**
The Tofogliflozin biological activity has been extensively evaluated in both cellular and animal models. Tofogliflozin In Vitro studies using tubular epithelial cells demonstrated that treatment with 3-30 nM for 24 hours inhibits high glucose-induced reactive oxygen species (ROS) generation and suppresses the gene expression of monocyte chemoattractant protein-1 (MCP-1). Furthermore, treatment with 3-30 nM for 8 days was found to inhibit apoptotic cell death induced by high glucose in these cells.
Tofogliflozin In Vivo research utilized db/db mice to assess its therapeutic potential. Oral administration of Tofogliflozin (0.1-10 mg/kg; once daily for 4 weeks) resulted in acute blood glucose reduction and a dose-dependent decrease in glycated hemoglobin, effectively improving hyperglycemia and glucose intolerance. Notably, doses of 3 and 10 mg/kg significantly prevented the decrease of IRI levels, while no significant differences were observed in food intake or body weight. For researchers requiring specific Tofogliflozin technical information or a detailed Tofogliflozin Data Sheet, these results highlight the compound’s efficacy in managing diabetic complications. In conclusion, Tofogliflozin is a potent and selective SGLT2 inhibitor that improves glycemic control and protects tubular cells from glucose-induced oxidative stress and apoptosis.
Keywords
Tofogliflozin, 1201913-82-7, CSG-452, CSG452, CSG 452, SGLT, Reactive Oxygen Species (ROS), Sodium-dependent glucose cotransporters, Inhibitor, inhibitor, inhibit
References
[1] Suzuki M, et al. Tofogliflozin, a potent and highly specific sodium/glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice. J Pharmacol Exp Ther. 2012 Jun;341(3):692-701.
[2] Ishibashi Y, et al. Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation. Horm Metab Res. 2016 Mar;48(3):191-5.