FBPase-IN-3

FBPase-IN-3 is an inhibitor targeting fructose-1,6-bisphosphatase (FBPase); by inhibiting the activity of this key rate-limiting enzyme in gluconeogenesis, it interferes with glucose production and can be used for metabolic regulation and research into mechanisms associated with type 2 diabetes.

FBPase:2.08 μM

Method: Recombinant human FBPase enzyme was used in Tris buffer (pH 7.5). Various concentrations (0.01, 0.1, 0.5, 1, 10, 20 μM) of FBPase-IN-3 were mixed with 10 μM FBPase and incubated at 37 °C for 10 min. The reaction was then initiated by adding 2 μM NADP⁺, 0.5 unit PGI, and 0.5 unit G6PDH, followed by incubation at 37 °C for 40 min. Absorbance was read at 340 nm, and FBPase inhibitory activity and IC₅₀ values were calculated.
Result: FBPase-IN-3 exhibited 81.8% inhibition of FBPase at 10 μM, with an IC₅₀ value of 2.08 μM^[1].

Method: ICR mice were fasted for 16 h, then orally administered FBPase-IN-3 (150 mg/kg). Blood was collected 1 h later for measurement of 0-min blood glucose, followed by oral administration of sodium pyruvate (2.0 g/kg). Blood samples were collected at 30 min and 90 min for blood glucose measurement, with metformin (150 mg/kg) as the positive control, in an oral pyruvate tolerance test (OPTT).
Result: Compared with the untreated control group, FBPase-IN-3 significantly reduced blood glucose levels in ICR mice at both 30 min and 90 min after pyruvate administration, with a glucose-lowering effect comparable to that of the metformin control group, indicating that FBPase-IN-3 possesses potent gluconeogenesis inhibitory activity and robust glucose-lowering efficacy^[1].