MK 0893 is a potent and selective Glucagon Receptor (GR) antagonist (IC50=6.6 nM) with competitive, reversible, high binding affinity and functional cAMP activity, which attenuates glucagon induced blood glucose elevation and reduces ambient glucose levels in acute and chronic mouse models.

VPAC2:>10000 nM, GCGR:15.7 nM (cAMP assay), VPAC1:>10000 nM, GIPR:1020 nM, GLP1 receptor:>10000 nM, GCGR:6.6 nM (binding), PAC1:9200 nM

MK 0893 is a potent, reversible, and competitive antagonist of the glucagon receptor (GCGR), exhibiting high binding affinity (IC₅₀ = 6.6 nM) and inhibitory activity in a cAMP functional assay (IC₅₀ = 15.7 nM). MK 0893 is highly selective for GCGR over other class B GPCRs, with IC₅₀ values of 1020 nM for GIPR, 9200 nM for PAC1, and >10000 nM for GLP-1R, VPAC1, and VPAC2[1].

In hGCGR transgenic mice and rhesus monkeys, MK 0893 effectively blunted glucagon-induced blood glucose elevation. In hGCGR ob/ob mice, single oral doses of 3 and 10 mg/kg reduced glucose AUC (0–6 h) by 32% and 39%, respectively. In hGCGR mice on a high-fat diet, daily feeding of 3 and 10 mg/kg for 10 days reduced blood glucose levels by 89% and 94%, respectively, relative to the difference between vehicle-treated and lean control mice[1].