2qtb | pdb_00002qtb
Human dipeptidyl peptidase iv/cd26 in complex with a 4-aryl cyclohexylalanine inhibitor
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| 2qtb, resolution 2.250Å | |||||||||||||
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| Ligands: | NAG, NA and 474 | ||||||||||||
| Gene: | DPP4, ADCP2, CD26 (Homo sapiens) | ||||||||||||
| Activity: | Dipeptidyl-peptidase IV, with EC number 3.4.14.5 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
A novel series of 4-arylcyclohexylalanine DPP-4 inhibitors was synthesized and tested for inhibitory activity as well as selectivity over the related proline-specific enzymes DPP-8 and DPP-9. Optimization of this series led to 28 (DPP-4 IC(50)=4.8 nM), which showed an excellent pharmacokinetic profile across several preclinical species. Evaluation of 28 in an oral glucose tolerance test demonstrated that this compound effectively reduced glucose excursion in lean mice.
About this Structure
2QTB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV., Kaelin DE, Smenton AL, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE, Duffy JL, Bioorg Med Chem Lett. 2007 Nov 1;17(21):5806-11. Epub 2007 Aug 26. PMID:17851076
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