2OQV

Human Dipeptidyl Peptidase IV (DPP4) with piperidine-constrained phenethylamine

Summary for 2OQV

• Entry DOI: 10.2210/pdb2oqv/pdb
• Related: 2OQI
• Descriptor: Dipeptidyl peptidase 4 (Dipeptidyl peptidase IV) (DPP IV), (3R,4R)-1-{6-[3-(METHYLSULFONYL)PHENYL]PYRIMIDIN-4-YL}-4-(2,4,5-TRIFLUOROPHENYL)PIPERIDIN-3-AMINE (2 entities in total)
• Functional Keywords: serine-peptidase, inhibitor, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Dipeptidyl peptidase 4 soluble form: Secreted . Cell membrane ; Single- pass type II membrane protein: P27487
• Total number of polymer chains: 2
• Total formula weight: 168967.16

Authors

Pei, Z.,Li, X.,von Geldern, T.W.,Longenecker, K.L.,Pireh, D.,Stewart, K.D. (deposition date: 2007-02-01, release date: 2007-04-24, Last modification date: 2024-10-16)

Primary citation

Pei, Z.,Li, X.,Geldern, T.W.,Longenecker, K.,Pireh, D.,Stewart, K.D.,Backes, B.J.,Lai, C.,Lubben, T.H.,Ballaron, S.J.,Beno, D.W.,Kempf-Grote, A.J.,Sham, H.L.,Trevillyan, J.M.
Discovery and Structure-Activity Relationships of Piperidinone- and Piperidine-Constrained Phenethylamines as Novel, Potent, and Selective Dipeptidyl Peptidase IV Inhibitors.
J.Med.Chem., 50:1983-1987, 2007

PubMed Abstract: Dipeptidyl peptidase IV (DPP4) inhibitors are emerging as a new class of therapeutic agents for the treatment of type 2 diabetes. They exert their beneficial effects by increasing the levels of active glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are two important incretins for glucose homeostasis. Starting from a high-throughput screening hit, we were able to identify a series of piperidinone- and piperidine-constrained phenethylamines as novel DPP4 inhibitors. Optimized compounds are potent, selective, and have good pharmacokinetic profiles.

PubMed: 17367123
DOI: 10.1021/jm061436d

Experimental method

X-RAY DIFFRACTION (2.8 Å)