3EIO

Crystal Structure Analysis of DPPIV Inhibitor

Summary for 3EIO

• Entry DOI: 10.2210/pdb3eio/pdb
• Descriptor: Dipeptidyl peptidase 4 soluble form, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-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, ... (6 entities in total)
• Functional Keywords: protein-inhibitor complex, aminopeptidase, cell membrane, glycoprotein, hydrolase, membrane, protease, secreted, serine protease, signal-anchor, transmembrane
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 174772.76

Authors

Ahn, J.H.,Lee, J.-O. (deposition date: 2008-09-17, release date: 2008-11-04, Last modification date: 2024-10-30)

Primary citation

Ahn, J.H.,Park, W.S.,Jun, M.A.,Shin, M.S.,Kang, S.K.,Kim, K.Y.,Rhee, S.D.,Bae, M.A.,Kim, K.R.,Kim, S.G.,Kim, S.Y.,Sohn, S.K.,Kang, N.S.,Lee, J.O.,Lee, D.H.,Cheon, H.G.,Kim, S.S.
Synthesis and biological evaluation of homopiperazine derivatives with beta-aminoacyl group as dipeptidyl peptidase IV inhibitors
Bioorg.Med.Chem.Lett., 18:6525-6529, 2008

PubMed Abstract: Compounds with homopiperazine skeleton are designed to find a potent DPP-IV inhibitor without inhibiting CYP. Thus a series of beta-aminoacyl-containing homopiperazine derivatives was synthesized and evaluated. Compounds with acid moiety were found to be potent inhibitors of DPP-IV without inhibiting CYP 3A4. More specifically, compound 7m showed nanomolar activity with no inhibition towards five subtypes of CYPs, was considered as a prototype for further derivatization. Based on its X-ray co-crystal structure with human DPP-IV, we identified compounds 7s and 7t which showed good in vitro activity, no CYP inhibition, and good selectivity.

PubMed: 18996694
DOI: 10.1016/j.bmcl.2008.10.076

Experimental method

X-RAY DIFFRACTION (2 Å)