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

ABSTRACT: A structure-activity relationship study of the imidazolyl-?-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.

SUBMITTER: He S

PROVIDER: S-EPMC4025728 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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

He Shuwen S Ye Zhixiong Z Truong Quang Q Shah Shrenik S Du Wu W Guo Liangqin L Dobbelaar Peter H PH Lai Zhong Z Liu Jian J Jian Tianying T Qi Hongbo H Bakshi Raman K RK Hong Qingmei Q Dellureficio James J Pasternak Alexander A Feng Zhe Z deJesus Reynalda R Yang Lihu L Reibarkh Mikhail M Bradley Scott A SA Holmes Mark A MA Ball Richard G RG Ruck Rebecca T RT Huffman Mark A MA Wong Frederick F Samuel Koppara K Reddy Vijay B VB Mitelman Stan S Tong Sharon X SX Chicchi Gary G GG Tsao Kwei-Lan KL Trusca Dorina D Wu Margaret M Shao Qing Q Trujillo Maria E ME Eiermann George J GJ Li Cai C Zhang Bei B BB Howard Andrew D AD Zhou Yun-Ping YP Nargund Ravi P RP Hagmann William K WK

ACS medicinal chemistry letters 20120507 6

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. ...[more]

PMID: 24900499

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