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- Title
118-LB: Preclinical Development of IDG-16177 as a Potent GPR40 Agonist for Treatment of Type 2 Diabetes.
- Authors
YOON, JONG MIN; KIM, DOHEE; LEE, DON-GIL; AN, KYUNG MI; LEE, MYONG JAE; HONG, CHANG-HEE; HONG, DAHAE; KWAK, HYUN-JUNG; JE, IN-GYU; SONG, HYO-JUNG
- Abstract
GPR40/FFAR1 is a G-protein-coupled receptor predominantly expressed in pancreatic β-cells. GPR40 agonists are known to stimulate insulin secretion and reduce circulating glucose levels in a glucose-dependent manner. We investigated IDG-16177(ID11014A) as a GPR40 agonist and confirmed this drug has linear pharmacokinetic properties and is more potent than fasiglifam from in vitro and in vivo studies. In vitro metabolic stability of IDG-16177 was evaluated in mouse, rat, dog, monkey and human microsomes. IDG-16177 was metabolized mainly by CYPs in mouse, rat, monkey and human while it was metabolized mainly by UGTs in dog. Oral bioavailability of IDG-16177 was 88.1 ~ 109.9% in SD rats. The Cmax and AUC values of IDG-16177 increased in a dose-proportional manner in the dose range of 1 ~ 10 mg/kg. IDG-16177 was also well exposed in monkeys after 3 mg/kg administration. Glucose lowering effect was determined by oral glucose tolerance test (OGTT) in Sprague-Dawley (SD) rats and in various type 2 diabetes rats, respectively. IDG-16177 showed dose-dependently improvement of glucose tolerance in a single dosing study using SD and Goto-Kakizaki (GK) rats. IDG-16177 1mg/kg showed more effective in glucose tolerance than fasiglifam 10mg/kg in repeated dosing study of Zucker Diabetic Fatty (ZDF) rats. In this study, Cmax,ss and AUCss of IDG-16177 showed approximately 10 times lower than those of fasiglifam. These results show that IDG-16177 might be an effective drug candidate for treatment of type 2 diabetes. Disclosure: J. Yoon: None. D. Kim: None. D. Lee: None. K. An: None. M. Lee: None. C. Hong: None. D. Hong: None. H. Kwak: None. I. Je: None. H. Song: None.
- Publication
Diabetes, 2020, Vol 69, pN.PAG
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db20-118-LB