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PDBsum entry 2w17

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Transferase PDB id
2w17
Jmol
Contents
Protein chain
279 a.a. *
Ligands
ACT
I19
Waters ×150
* Residue conservation analysis
PDB id:
2w17
Name: Transferase
Title: Cdk2 in complex with the imidazole pyrimidine amide, compound (s)-8b
Structure: Cell division protein kinase 2. Chain: a. Synonym: cyclin dependent kinase 2, p33 protein kinase. Engineered: yes. Other_details: acetylation at n-terminal methionine
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.
Resolution:
2.15Å     R-factor:   0.244     R-free:   0.300
Authors: C.D.Jones,D.M.Andrews,A.J.Barker,K.Blades,P.Daunt,S.East,C.G M.A.Graham,K.M.Johnson,S.A.Loddick,H.M.Mcfarland,A.Mcgregor D.A.Rudge,P.B.Simpson,M.L.Swain,K.Y.Tam,J.A.Tucker,M.Walker C.Brassington,H.Haye,E.Mccall
Key ref: C.D.Jones et al. (2008). The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem Lett, 18, 6369-6373. PubMed id: 18996007 DOI: 10.1016/j.bmcl.2008.10.102
Date:
15-Oct-08     Release date:   04-Nov-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
278 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.22  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cyclin-dependent protein kinase holoenzyme complex   15 terms 
  Biological process     regulation of gene silencing   27 terms 
  Biochemical function     nucleotide binding     12 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2008.10.102 Bioorg Med Chem Lett 18:6369-6373 (2008)
PubMed id: 18996007  
 
 
The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing.
C.D.Jones, D.M.Andrews, A.J.Barker, K.Blades, P.Daunt, S.East, C.Geh, M.A.Graham, K.M.Johnson, S.A.Loddick, H.M.McFarland, A.McGregor, L.Moss, D.A.Rudge, P.B.Simpson, M.L.Swain, K.Y.Tam, J.A.Tucker, M.Walker.
 
  ABSTRACT  
 
The development of a novel series of imidazole pyrimidine amides as cyclin-dependent kinase (CDK) inhibitors is described. Optimisation of inhibitory potency against multiple CDK's (1, 2 and 9) resulted in imidazole pyrimidine amides with potent in vitro anti-proliferative effects against a range of cancer cell lines. Excellent physiochemical properties and large margins against inhibition of CYP isoforms and the hERG ion channel were achieved by modification of lipophilicity and amine basicity. A candidate with disease model activity in human cancer cell line xenografts and with suitable physiochemical and pharmacokinetic profiles for intravenous (i.v.) dosing was selected for further development as AZD5597.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21333571 C.Fang, Z.Xiao, and Z.Guo (2011).
Generation and validation of the first predictive pharmacophore model for cyclin-dependent kinase 9 inhibitors.
  J Mol Graph Model, 29, 800-808.  
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