Pyrazolo[3,4-b]quinoxalines. A new class of cyclin-dependent kinases inhibitors.
Bioorg Med Chem
; 10(7): 2177-84, 2002 Jul.
Article
em En
| MEDLINE
| ID: mdl-11983514
ABSTRACT
Protein kinases are involved in most physiological processes and in numerous diseases. Therefore, inhibitors of protein kinases have therefore a wide therapeutic potential. While screening for inhibitors of cyclin-dependent kinases (CDK's) and glycogen synthase kinase-3 (GSK-3), we identified pyrazolo[3,4-b]quinoxalines as sub-micromolar inhibitors of CDK1/cyclin B. A preliminary structure-activity relationship study suggests that this family of compounds can be optimized to inhibit CDK's and GSK-3. Compounds were tested for their anti-proliferative activity and the results show that several of them displayed a significant inhibitory effect on CDK1/cyclin B. The most active compound (1) was also tested against the brain kinases CDK5/p25 and GSK-3, and proved to be a good inhibitor of both of them. On the contrary, none of the compounds showed any activity in the CDC25 phosphatase assay. As an additional approach, affinity chromatography on immobilized pyrazolo[3,4-b]quinoxalines will be used to identify the intracellular targets of this family of compounds.
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Quinoxalinas
/
Quinases Ciclina-Dependentes
/
Inibidores Enzimáticos
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article