FBPase-IN-1

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.

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].

References:
[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.