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PDBsum entry 2uzd
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References listed in PDB file
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Key reference
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Title
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Discovery of a potent cdk2 inhibitor with a novel binding mode, Using virtual screening and initial, Structure-Guided lead scoping.
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Authors
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C.M.Richardson,
C.L.Nunns,
D.S.Williamson,
M.J.Parratt,
P.Dokurno,
R.Howes,
J.Borgognoni,
M.J.Drysdale,
H.Finch,
R.E.Hubbard,
P.S.Jackson,
P.Kierstan,
G.Lentzen,
J.D.Moore,
J.B.Murray,
H.Simmonite,
A.E.Surgenor,
C.J.Torrance.
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Ref.
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Bioorg Med Chem Lett, 2007,
17,
3880-3885.
[DOI no: ]
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PubMed id
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Abstract
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Virtual screening against a pCDK2/cyclin A crystal structure led to the
identification of a potent and novel CDK2 inhibitor, which exhibited an unusual
mode of interaction with the kinase binding motif. With the aid of X-ray
crystallography and modelling, a medicinal chemistry strategy was implemented to
probe the interactions seen in the crystal structure and to establish SAR. A
fragment-based approach was also considered but a different, more conventional,
binding mode was observed. Compound selectivity against GSK-3beta was improved
using a rational design strategy, with crystallographic verification of the CDK2
binding mode.
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