3LE6

The structure of cyclin dependent kinase 2 (CKD2) with a pyrazolobenzodiazepine inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Pyrazolobenzodiazepines: part I. Synthesis and SAR of a potent class of kinase inhibitors.

Liu, J.J.Daniewski, I.Ding, Q.Higgins, B.Ju, G.Kolinsky, K.Konzelmann, F.Lukacs, C.Pizzolato, G.Rossman, P.Swain, A.Thakkar, K.Wei, C.C.Miklowski, D.Yang, H.Yin, X.Wovkulich, P.M.

(2010) Bioorg Med Chem Lett 20: 5984-5987

  • DOI: https://doi.org/10.1016/j.bmcl.2010.08.079
  • Primary Citation of Related Structures:  
    3LE6

  • PubMed Abstract: 

    A novel series of pyrazolobenzodiazepines 3 has been identified as potent inhibitors of cyclin-dependent kinase 2 (CDK2). Their synthesis and structure-activity relationships (SAR) are described. Representative compounds from this class reversibly inhibit CDK2 activity in vitro, and block cell cycle progression in human tumor cell lines. Further exploration has revealed that this class of compounds inhibits several kinases that play critical roles in cancer cell growth and division as well as tumor angiogenesis. Together, these properties suggest a compelling basis for their use as antitumor agents.


  • Organizational Affiliation

    Discovery Chemistry, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. jin-jun.liu@roche.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 
Gene Names: CDK2
EC: 2.7.11.22
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
2BZ
Query on 2BZ

Download Ideal Coordinates CCD File 
B [auth A]5-(2-chlorophenyl)-3-methyl-7-nitropyrazolo[3,4-b][1,4]benzodiazepine
C17 H10 Cl N5 O2
NKUOWCWVEBHJCR-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
2BZ PDBBind:  3LE6 IC50: 35 (nM) from 1 assay(s)
Binding MOAD:  3LE6 IC50: 35 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.22α = 90
b = 70.964β = 90
c = 72.211γ = 90
Software Package:
Software NamePurpose
CNXrefinement
HKL-2000data reduction
HKL-2000data scaling
CNXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-11-17
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations