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PDBsum entry 2w17
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Cdk2 in complex with the imidazole pyrimidine amide, compound (s)-8b
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Structure:
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Cell division protein kinase 2. Chain: a. Synonym: cyclin dependent kinase 2, p33 protein kinase. Engineered: yes. Other_details: acetylation at n-terminal methionine
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.
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Resolution:
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2.15Å
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R-factor:
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0.244
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R-free:
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0.300
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Authors:
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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, C.Brassington,H.Haye,E.Mccall
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Key ref:
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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:
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Date:
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15-Oct-08
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Release date:
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04-Nov-08
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PROCHECK
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Headers
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References
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P24941
(CDK2_HUMAN) -
Cyclin-dependent kinase 2 from Homo sapiens
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Seq:
Struc:
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298 a.a.
278 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.7.11.22
- cyclin-dependent kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Bioorg Med Chem Lett
18:6369-6373
(2008)
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PubMed id:
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The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing.
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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.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.Fang,
Z.Xiao,
and
Z.Guo
(2011).
Generation and validation of the first predictive pharmacophore model for cyclin-dependent kinase 9 inhibitors.
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J Mol Graph Model,
29,
800-808.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
