GRA Ex-25

Description: GRA Ex-25 is a novel and potent inhibitor of glucagon receptor with IC50 of 56 and 55 nM for rat and human glucagon receptors, respectively. GRA Ex-25 binds a human glucagon receptor (h-GlucRbind) with Ki of 63 nM and a moderate glucagon induced adenylate cyclase inhibition (h-GlucRcyclase) with Ki of 254 nM under our assay conditions. GRA Ex-25 has similar affinity to the rat and human glucagon receptors (IC50=56 and 55 nM, respectively). GRA Ex-25 (3 mg/kg, i.v.) significantly reduces blood glucose caused by exogenous administration of glucagon in rat model. GRA Ex-25 is able to inhibit the rise in blood glucose levels elicited by exogenous administered glucagon, most likely because of the direct inhibition of glucagon stimulated hepatic glucose output.

References: J Med Chem. 2007 Jan 11; 50(1):113-28; Bioorg Med Chem Lett. 2004 May 3; 14(9):2047-50.

SMILES Code: C[C](C1CC[CH](N(C(NC2C=CC(OC(F)(F)F)=CC=2)=O)CC2C=CC(C(NCCC(O)=O)=O)=CC=2)CC1)(C)C