Luseogliflozin (TS 071) hydrate, a second-generation sodium-glucose co-transporter 2 (SGLT2) inhibitor, exhibits selective potency and oral activity, with an IC50 of 2.26 nM. This compound is utilized in research for the treatment of type 2 diabetes mellitus (T2DM).

SGLT2:2.26 nM (IC50)

Luseogliflozin enhances beta cell proliferation by activating the FoxM1/PLK1/CENP-A pathway through signaling molecules that do not depend on the insulin/IGF-1 receptors. This effect is evident in OSI-906-treated mice. Furthermore, a Cell Viability Assay conducted on βIRKO, IRS1KO, and IRS2KO beta cells, with a concentration of 100 nM and incubation times of 24 and 48 hours, demonstrated that serum from OSI-906+Luseogliflozin-treated groups significantly improved cell viability compared to the OSI-906 alone group, including in insulin receptor (IR)-deficient βIRKO beta cells.

Administering Luseogliflozin (10 mg/kg/daily via oral gavage) significantly alleviated hyperglycemia, while not affecting hyperinsulinemia, in C57BL/6J male mice aged 8 weeks old exposed to OSI-906 (45 mg/kg). Specifically, Luseogliflozin treatment effectively mitigated the hyperglycemia provoked by OSI-906[2]. This was achieved with a daily dosage of 10 mg/kg, administered orally through gavage for a duration of 7 days between 08:00 and 09:00 hours, demonstrating the compound's therapeutic potential in ameliorating OSI-906-induced hyperglycemia.