Novel Series of Potent Glucokinase Activators Leading to the Discovery of AM-2394.
ACS Med Chem Lett
; 7(7): 714-8, 2016 Jul 14.
Article
in En
| MEDLINE
| ID: mdl-27437083
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ACS Med Chem Lett
Year:
2016
Type:
Article
Affiliation country:
United States