Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping.
Bioorg Med Chem Lett
; 17(14): 3880-5, 2007 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-17570665
ABSTRACT
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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Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Proteínas Quinasas
/
Quinasa 2 Dependiente de la Ciclina
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Año:
2007
Tipo del documento:
Article