2OQV

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.309 
  • R-Value Work: 0.243 
  • R-Value Observed: 0.246 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Discovery and Structure-Activity Relationships of Piperidinone- and Piperidine-Constrained Phenethylamines as Novel, Potent, and Selective Dipeptidyl Peptidase IV Inhibitors.

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.

(2007) J Med Chem 50: 1983-1987

  • DOI: https://doi.org/10.1021/jm061436d
  • Primary Citation of Related Structures:  
    2OQI, 2OQV

  • 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.


  • Organizational Affiliation

    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA. zhonghua.pei@abbott.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl peptidase 4 (Dipeptidyl peptidase IV) (DPP IV)
A, B
726Homo sapiensMutation(s): 0 
Gene Names: DPP4ADCP2CD26
EC: 3.4.14.5
UniProt & NIH Common Fund Data Resources
Find proteins for P27487 (Homo sapiens)
Explore P27487 
Go to UniProtKB:  P27487
PHAROS:  P27487
GTEx:  ENSG00000197635 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27487
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MA9
Query on MA9

Download Ideal Coordinates CCD File 
C [auth A](3R,4R)-1-{6-[3-(METHYLSULFONYL)PHENYL]PYRIMIDIN-4-YL}-4-(2,4,5-TRIFLUOROPHENYL)PIPERIDIN-3-AMINE
C22 H21 F3 N4 O2 S
GOBIXGZJSMAOFV-QRWLVFNGSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
MA9 PDBBind:  2OQV Ki: 4 (nM) from 1 assay(s)
BindingDB:  2OQV Ki: 4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.309 
  • R-Value Work: 0.243 
  • R-Value Observed: 0.246 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.012α = 90
b = 118.203β = 90
c = 232.517γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
HKL-2000data reduction
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-04-24
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description
  • Version 1.4: 2023-12-27
    Changes: Data collection, Database references, Derived calculations, Refinement description