2oph
From Proteopedia
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| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | DPP4, ADCP2, CD26 (Homo sapiens) | ||||||
| Activity: | Dipeptidyl-peptidase IV, with EC number 3.4.14.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human dipeptidyl peptidase IV in complex with an alpha amino acid inhibitor
Overview
A novel series of 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives were designed and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4). The phenylalanine series afforded compounds such as 10 that were potent and selective (DPP-4, IC(50)=28nM), but exhibited limited oral bioavailability. The corresponding cyclohexylalanine derivatives such as 25 afforded improved PK exposure and efficacy in a murine OGTT experiment. The X-ray crystal structure of 25 bound to the DPP-4 active site is presented.
About this Structure
2OPH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV., Duffy JL, Kirk BA, Wang L, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE, Bioorg Med Chem Lett. 2007 May 15;17(10):2879-85. Epub 2007 Feb 25. PMID:17350841
Page seeded by OCA on Thu Mar 20 18:02:46 2008
Categories: Dipeptidyl-peptidase IV | Homo sapiens | Single protein | Duffy, J L. | Scapin, G. | Weber, A E. | 277 | NA | NAG | Alpha/beta | Beta-propeller | Dimer | Selective inhibitor | Type 2 diabetes
