2QT9

Human dipeptidyl peptidase iv/cd26 in complex with a 4-aryl cyclohexylalanine inhibitor

Summary for 2QT9

• Entry DOI: 10.2210/pdb2qt9/pdb
• Related: 2QTB
• Descriptor: Dipeptidyl peptidase 4, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: alpha/beta, beta-propeller, dimer, aminopeptidase, glycoprotein, hydrolase, membrane, protease, secreted, serine protease, signal-anchor, transmembrane
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 182793.51

Authors

Scapin, G. (deposition date: 2007-08-01, release date: 2007-11-06, Last modification date: 2024-10-30)

Primary citation

Kaelin, D.E.,Smenton, A.L.,Eiermann, G.J.,He, H.,Leiting, B.,Lyons, K.A.,Patel, R.A.,Patel, S.B.,Petrov, A.,Scapin, G.,Wu, J.K.,Thornberry, N.A.,Weber, A.E.,Duffy, J.L.
4-Arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV.
Bioorg.Med.Chem.Lett., 17:5806-5811, 2007

PubMed Abstract: 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.

PubMed: 17851076
DOI: 10.1016/j.bmcl.2007.08.049

Experimental method

X-RAY DIFFRACTION (2.1 Å)