2-(1,3-thiazol-2-yldisulfanyl)-1,3-thiazole

FBPase-IN-1 is a potent FBPase (Fructose-1,6-bisphosphatase) inhibitor for Type 2 diabetes (T2D) study with an IC50 of 0.22 μM. FBPase-IN-1 can reduce blood glucose levels and ameliorate glucose tolerance. FBPase-IN-1 modifies the C128 site, regulates the N125-S124-S123 allosteric pathway of FBPase and affects the catalytic activity of FBPase[1].

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

IC50: 0.22 μM (FBPase)[1]

FBPase-IN-1 (compund 3a) (1.5625-200 μM, 48 hours) shows a low cytotoxicity with an IC50 of 75.08 μM[1]. FBPase-IN-1 (0-45 min) inhibits FBPase in a time-dependent manner, with IC50 decreasing from 0.28 to 0.09 μM, shows FBPase-IN-1 is an irreversible covalent inhibitor of FBPase[1].

FBPase-IN-1 (12 h-fasted ICR mouse, n = 6, male, 25 mg/kg, IP) shows good FBPase inhibitory activity (IC50 = 0.22 μM), satisfying glucose-lowering effect in vivo (54% reduction in blood glucose at 25 mg/kg)[1]. FBPase-IN-1 (6 or 7 weeks, ICR mice, n = 6, male, 25 mg/kg, IP for 4 hours, once) reduces blood glucose levels by targeting FBPase and inhibiting the GNG process[1]. Animal Model: ICR mouse (12 h-fasted, n = 6, male)[1] Dosage: 25 mg/kg Administration: IP, once Result: Lowered glucose. Animal Model: ICR mice (6 or 7 weeks, n = 6, male)[1] Dosage: 25 mg/kg Administration: IP, for 4 h, once Result: Reduced blood glucose levels by targeting FBPase and inhibiting the GNG process.

[1]. Xu YX, Huang YY, Song RR, et al. Development of disulfide-derived fructose-1,6-bisphosphatase (FBPase) covalent inhibitors for the treatment of type 2 diabetes. Eur J Med Chem. 2020; 203: 112500.