tcsc0324 MK 0893

MK 0893 is a potent, selective glucagon receptor antagonist with IC₅₀ of 6.6 nM, and > 200 fold selectivity against GIPR, PAC1, GLP-1R, VPAC1 and VPAC2.

IC50 & Target: IC50: 6.6 nM (glucagon receptor)

In Vitro: MK 0893 is selective for glucagon receptor relative to other family B GPCRs, showing IC₅₀ values of 1020 nM for GIPR, 9200 nM for PAC1, and >10000 nM for GLP-1R, VPAC1, and VPAC2. MK 0893 is active against the rhesus monkey GCGR, showing an IC₅₀ of 56 nM in a cAMP assay with CHO cells expressing the rhesus GCGR^[1].

In Vivo: MK 0893 blunts glucagon-induced glucose elevation in hGCGR mice and rhesus monkeys. It also lowers ambient glucose levels in both acute and chronic mouse models: in hGCGR ob/ob mice it reduces glucose (AUC 0-6 h) by 32% and 39% at 3 and 10 mpk single doses, respectively. In hGCGR mice on a high fat diet, MK 0893 at 3, and 10 mpk po in feed lowers blood glucose levels by 89% and 94% at day 10, respectively, relative to the difference between the vehicle control and lean hGCGR mice^[1].