2fjp
From Proteopedia
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Human dipeptidyl peptidase IV/CD26 in complex with an inhibitor
Overview
A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1 ,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC(50) = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes.
About this Structure
2FJP is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Dipeptidyl-peptidase IV, with EC number 3.4.14.5 Full crystallographic information is available from OCA.
Reference
(2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1 ,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes., Edmondson SD, Mastracchio A, Mathvink RJ, He J, Harper B, Park YJ, Beconi M, Di Salvo J, Eiermann GJ, He H, Leiting B, Leone JF, Levorse DA, Lyons K, Patel RA, Patel SB, Petrov A, Scapin G, Shang J, Roy RS, Smith A, Wu JK, Xu S, Zhu B, Thornberry NA, Weber AE, J Med Chem. 2006 Jun 15;49(12):3614-27. PMID:16759103
Page seeded by OCA on Thu Feb 21 17:22:05 2008
Categories: Dipeptidyl-peptidase IV | Homo sapiens | Single protein | Becker, J W. | Patel, S B. | Scapin, G. | NAG | S14 | Alpha/beta | Beta-propeller | Dimer
