2OAE: Crystal Structure Of Rat Dipeptidyl Peptidase (dppiv) With Thiazole- Based Peptide Mimetic #31

Citation:
Abstract
A novel series of pyrrolidine-constrained phenethylamines were developed as dipeptidyl peptidase IV (DPP4) inhibitors for the treatment of type 2 diabetes. The cyclohexene ring of lead-like screening hit 5 was replaced with a pyrrolidine to enable parallel chemistry, and protein co-crystal structural data guided the optimization of N-substituents. Employing this strategy, a >400x improvement in potency over the initial hit was realized in rapid fashion. Optimized compounds are potent and selective inhibitors with excellent pharmacokinetic profiles. Compound 30 was efficacious in vivo, lowering blood glucose in ZDF rats that were allowed to feed freely on a mixed meal.
PDB ID: 2OAEDownload
MMDB ID: 44677
PDB Deposition Date: 2006/12/15
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 2OAE: dimeric; determined by author and by software (PISA)
Molecular Components in 2OAE
Label Count Molecule
Proteins (2 molecules)
2
Dipeptidyl Peptidase 4(Gene symbol: Dpp4)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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