Glucokinase Activator II

A cell-permeable compound that reduces glucokinase Km for glucose (EC₅₀ = 120 nM & 350 nM, for human and rat enzyme). Enhances insulin secretion from INS-1 cells upon glucose exposure.

A cell-permeable indazole derivative that reduces glucokinase K_m for glucose (EC₅₀ = 120 nM and 350 nM, respectively, for human and rat enzyme) and effectively enhances insulin secretion from rat insulinima INS-1 cells upon 5 mM glucose exposure (EC₅₀ = 170 nM). Shown to be orally available in rats (F = 69%; C_max = 1490 ng/mL; t_1/2 = 2.6 hr; AUC = 5440 ng·hr/mL; 5 mg/kg p.o.) and exhibit blood glucose lowering efficacy in OGTT (2 g/kg oral glucose challenge 1 h after single drug oral dosage) test on fasted rats (22% reduction of AUC; 250 mg/kg p.o.) in vivo.

Cell permeable: yes

Primary Target
Glucokinase

Following reconstitution, aliquot and freeze (=2-°C). Stock solutions are stable for up to 3 months at -20°C.

Pfefferkorn, J. A., et al. 2012. Bioorg. Med. Chem. Lett.22, 7100.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)