The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes

ACS Med Chem Lett. 2012 May 7;3(6):484-9. doi: 10.1021/ml300063m. eCollection 2012 Jun 14.

Abstract

A structure-activity relationship study of the imidazolyl-β-tetrahydrocarboline series identified MK-4256 as a potent, selective SSTR3 antagonist, which demonstrated superior efficacy in a mouse oGTT model. MK-4256 reduced glucose excursion in a dose-dependent fashion with maximal efficacy achieved at doses as low as 0.03 mg/kg po. As compared with glipizide, MK-4256 showed a minimal hypoglycemia risk in mice.

Keywords: SSTR3; antagonist; type 2 diabetes; β-tetrahydrocarboline.