Title : Unique binding mode of Evogliptin with human dipeptidyl peptidase IV - Lee_2017_Biochem.Biophys.Res.Commun_494_452 |
Author(s) : Lee HK , Kim MK , Kim HD , Kim HJ , Kim JW , Lee JO , Kim CW , Kim EE |
Ref : Biochemical & Biophysical Research Communications , 494 :452 , 2017 |
Abstract :
Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2 diabetes in South Korea. In this study, we report the crystal structures of Evogliptin, DA-12166, and DA-12228 (S,R diastereomer of Evogliptin) complexed to human DPP4. Analysis of both the structures and inhibitory activities suggests that the binding of the trifluorophenyl moiety in the S1 pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S2 extensive subsite, and that the multiple hydrogen bonds made by the (R)-beta-amine group in the S2 pocket and the contacts made by the (R)-tert-butyl group with Arg125 contribute to the high potency observed for Evogliptin. |
PubMedSearch : Lee_2017_Biochem.Biophys.Res.Commun_494_452 |
PubMedID: 29061303 |
Gene_locus related to this paper: human-DPP4 |
Inhibitor | DA-12166 DA-12228 Evogliptin |
Gene_locus | human-DPP4 |
Structure | 5Y7H 5Y7J 5Y7K |
Lee HK, Kim MK, Kim HD, Kim HJ, Kim JW, Lee JO, Kim CW, Kim EE (2017)
Unique binding mode of Evogliptin with human dipeptidyl peptidase IV
Biochemical & Biophysical Research Communications
494 :452
Lee HK, Kim MK, Kim HD, Kim HJ, Kim JW, Lee JO, Kim CW, Kim EE (2017)
Biochemical & Biophysical Research Communications
494 :452