2BTR

STRUCTURE OF CDK2 COMPLEXED WITH PNU-198873


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure-Based Drug Design to the Discovery of New 2-Aminothiazole Cdk2 Inhibitors.

Vulpetti, A.Casale, E.Roletto, F.Amici, R.Villa, M.Pevarello, P.

(2006) J Mol Graph Model 24: 341

  • DOI: https://doi.org/10.1016/j.jmgm.2005.09.012
  • Primary Citation of Related Structures:  
    2BTR, 2BTS

  • PubMed Abstract: 

    N-(5-Bromo-1,3-thiazol-2-yl)butanamide (compound 1) was found active (IC50=808 nM) in a high throughput screening (HTS) for CDK2 inhibitors. By exploiting crystal structures of several complexes between CDK2 and inhibitors and applying structure-based drug design (SBDD), we rapidly discovered a very potent and selective CDK2 inhibitor 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide (compound 4, IC50=20 nM). The syntheses, structure-based analog design, kinases inhibition data and X-ray crystallographic structures of CDK2/inhibitor complexes are reported.


  • Organizational Affiliation

    Department of Chemistry, Nerviano Medical Sciences, Discovery Research Oncology, Viale Pasteur 10, 20014 Nerviano (MI), Italy. anna.vulpetti@nervianoms.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CELL DIVISION PROTEIN KINASE 2298Homo sapiensMutation(s): 0 
EC: 2.7.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for P24941 (Homo sapiens)
Explore P24941 
Go to UniProtKB:  P24941
PHAROS:  P24941
GTEx:  ENSG00000123374 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP24941
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
U73
Query on U73

Download Ideal Coordinates CCD File 
B [auth A]N-(5-ISOPROPYL-THIAZOL-2-YL)-2-PYRIDIN-3-YL-ACETAMIDE
C13 H15 N3 O S
WQZOOPQQADNJEG-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
U73 PDBBind:  2BTR IC50: 95 (nM) from 1 assay(s)
Binding MOAD:  2BTR IC50: 95 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.215α = 90
b = 71.615β = 90
c = 71.588γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-11-09
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2019-04-03
    Changes: Data collection, Other, Source and taxonomy