2fjp

From Proteopedia

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Revision as of 20:00, 12 November 2007

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spinqualitylabelsall models 2fjp, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 NAG and S14 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

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