Novel Series of Potent Glucokinase Activators Leading to the Discovery of AM-2394.
Basic Information
ID: ALA4425170
Journal: ACS Med Chem Lett
Title: Novel Series of Potent Glucokinase Activators Leading to the Discovery of AM-2394.
Authors: Dransfield PJ, Pattaropong V, Lai S, Fu Z, Kohn TJ, Du X, Cheng A, Xiong Y, Komorowski R, Jin L, Conn M, Tien E, DeWolf WE, Hinklin RJ, Aicher TD, Kraser CF, Boyd SA, Voegtli WC, Condroski KR, Veniant-Ellison M, Medina JC, Houze J, Coward P.
Abstract: Glucokinase (GK) catalyzes the phosphorylation of glucose to glucose-6-phosphate. We present the structure-activity relationships leading to the discovery of AM-2394, a structurally distinct GKA. AM-2394 activates GK with an EC50 of 60 nM, increases the affinity of GK for glucose by approximately 10-fold, exhibits moderate clearance and good oral bioavailability in multiple animal models, and lowers glucose excursion following an oral glucose tolerance test in an ob/ob mouse model of diabetes.
CiteXplore: 27437083
DOI: 10.1021/acsmedchemlett.6b00140
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