2DS1

Human cyclin dependent kinase 2 complexed with the CDK4 inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.225 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structure-based drug design of a highly potent CDK1,2,4,6 inhibitor with novel macrocyclic quinoxalin-2-one structure

Kawanishi, N.Sugimoto, T.Shibata, J.Nakamura, K.Masutani, K.Ikuta, M.Hirai, H.

(2006) Bioorg Med Chem Lett 16: 5122-5126

  • DOI: https://doi.org/10.1016/j.bmcl.2006.07.026
  • Primary Citation of Related Structures:  
    2DS1

  • PubMed Abstract: 

    The design of a novel series of cyclin-dependent kinase (CDK) inhibitors containing a macrocyclic quinoxaline-2-one is reported. Structure-based drug design and optimization from the starting point of diarylurea 2, which we previously reported as a moderate CDK1,2,4,6 inhibitor [J. Biol.Chem.2001, 276, 27548], led to the discovery of potent CDK1,2,4,6 inhibitor that were suitable for iv administration for in vivo study.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Banyu Tsukuba Research Institute in collaboration with Merck Research Laboratories, Okubo-3, Tsukuba 300-2611, Ibaraki, Japan. nobuhiko_kawanishi@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division protein kinase 2298Homo sapiensMutation(s): 3 
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
1CD
Query on 1CD

Download Ideal Coordinates CCD File 
B [auth A](13R,15S)-13-METHYL-16-OXA-8,9,12,22,24-PENTAAZAHEXACYCLO[15.6.2.16,9.1,12,15.0,2,7.0,21,25]HEPTACOSA-1(24),2,4,6,17(25 ),18,20-HEPTAENE-23,26-DIONE
C22 H21 N5 O3
KBLPHMRCKHFBJB-OLZOCXBDSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
1CD PDBBind:  2DS1 IC50: 3.4 (nM) from 1 assay(s)
BindingDB:  2DS1 IC50: 3.4 (nM) from 1 assay(s)
Binding MOAD:  2DS1 IC50: 3.4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.225 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.05α = 90
b = 71.22β = 90
c = 53.58γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2007-06-19 
  • Deposition Author(s): Ikuta, M.

Revision History  (Full details and data files)

  • Version 1.0: 2007-06-19
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-11-10
    Changes: Database references, Derived calculations, Structure summary
  • Version 1.4: 2023-10-25
    Changes: Data collection, Refinement description