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

Authors :
He S
Ye Z
Truong Q
Shah S
Du W
Guo L
Dobbelaar PH
Lai Z
Liu J
Jian T
Qi H
Bakshi RK
Hong Q
Dellureficio J
Pasternak A
Feng Z
deJesus R
Yang L
Reibarkh M
Bradley SA
Holmes MA
Ball RG
Ruck RT
Huffman MA
Wong F
Samuel K
Reddy VB
Mitelman S
Tong SX
Chicchi GG
Tsao KL
Trusca D
Wu M
Shao Q
Trujillo ME
Eiermann GJ
Li C
Zhang BB
Howard AD
Zhou YP
Nargund RP
Hagmann WK
Source :
ACS medicinal chemistry letters [ACS Med Chem Lett] 2012 May 07; Vol. 3 (6), pp. 484-9. Date of Electronic Publication: 2012 May 07 (Print Publication: 2012).
Publication Year :
2012

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.

Details

Language :
English
ISSN :
1948-5875
Volume :
3
Issue :
6
Database :
MEDLINE
Journal :
ACS medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
24900499
Full Text :
https://doi.org/10.1021/ml300063m