Background:

IC50: 3.4 μM

Fructose 1,6-bisphosphatase-1 Inhibitor is a fructose 1,6-bisphosphatase-1 inhibitor.

Fructose 1,6-bisphosphatase-1 (FBPase-1), an enzyme catalyzing the conversion of fructose-1,6-bisphosphate to fructose 6-phosphate, is one of the rate-limiting steps in gluconeogenesis. Excess hepatic fructose 1,6-bisphosphatase-1 activity contributes to hyperglycemia in patients.

In vitro: In a confirmatory assay, production of fructose-6-phosphate was monitored to give 6-phosphoglucono-d-lactone. The concomitant reduction of NADP to NADPH was also monitored. Fructose 1,6-bisphosphatase-1 Inhibitor was found to exhibit similar potency in these two distinct assays of FBPase-1 activity. Moreover, the ‘coupled’ assay format produced time-resolved data that might be subjected to kinetic analysis, indicating a Ki of 1.1μM for Fructose 1,6-bisphosphatase-1 Inhibitor. Fructose 1,6-bisphosphatase-1 Inhibitor also functioned as expected in a cellular model of glucose production. In an assay, rat hepatoma cells were starved of nutrients, making them highly dependent on the processing of pyruvate and lactate. Glucose production was measured over a three-hour period and the decrease in glucose that occurs with increasing doses of Fructose 1,6-bisphosphatase-1 Inhibitor was indicative of its ability to block gluconeogenesis by inhibiting FBPase-1 [1].

In vivo: So far, there is no animal data reported.

Clinical trial: Up to now, Fructose 1,6-bisphosphatase-1 Inhibitor is still in the preclinical development stage.

Reference:
[1] C.  Lai, R. J. Gum, M. Daly, et al. Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorganic & Medicinal Chemistry Letters 16(7), 1807-1810 (2006).