Show simple item record

dc.contributor.authorCanduri, Fernanda [UNESP]
dc.contributor.authorde Azevedo, Walter Filgueira [UNESP]
dc.identifier.citationCurrent Computer-aided Drug Design. Sharjah: Bentham Science Publ Ltd, v. 1, n. 1, p. 53-64, 2005.
dc.description.abstractCell cycle progression is tightly controlled by the activity of cyclin-dependent kinases (CDKs). CDKs are inactive as monomers, and activation requires binding to cyclins, a diverse family of proteins whose levels oscillate during the cell cycle, and phosphorylation by CDK-activating kinase (CAK) on a specific threonine residue. The central role of CDKs in cell cycle regulation makes them a promising target for studying inhibitory molecules that can modify the degree of cell proliferation, the discovery of specific inhibitors of CDKs such as polyhydroxylated flavones has opened the way to investigation and design of antimitotic compounds. A chlorinated form, flavopiridol, is currently in phase II clinical trials as a drug against breast tumors. The aromatic portion of the inhibitor binds to the adenine-binding pocket of CDK2, and the position of the phenyl group of the inhibitor enables the inhibitor to make contacts with the enzyme not observed in the ATP complex structure, the analysis of the position of this phenyl ring not only explains the great differences of kinase inhibition among the flavonoid inhibitors but also explains the specificity of roscovitine and olomoucine to inhibit CDK2. There is strong interest in CDKs inhibitors that could play an important role in the discovery of a new family of antitumor agents. The crystallographic analysis together with bioinformatics studies of CDKs are generating new information about the structural basis for inhibition of CDKs. The relevant structural features that may guide the structure based-design of a new generation of CDK inhibitors are discussed in this review.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.publisherBentham Science Publ Ltd
dc.relation.ispartofCurrent Computer-aided Drug Design
dc.sourceWeb of Science
dc.subjectdrug designpt
dc.titleStructural Basis for Interaction of Inhibitors with Cyclin-Dependent Kinase 2en
dcterms.rightsHolderBentham Science Publ Ltd
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.description.affiliationUNESP, Dept Fis, BR-15054000 Sao Jose do Rio Preto, SP, Brazil
dc.description.affiliationUNESP, Programa Posgrad Biofis Mol, BR-15054000 Sao Jose do Rio Preto, SP, Brazil
dc.description.affiliationUnespUNESP, Dept Fis, BR-15054000 Sao Jose do Rio Preto, SP, Brazil
dc.description.affiliationUnespUNESP, Programa Posgrad Biofis Mol, BR-15054000 Sao Jose do Rio Preto, SP, Brazil
dc.rights.accessRightsAcesso restrito
dc.description.sponsorshipIdFAPESP: 01/07532-0
dc.description.sponsorshipIdFAPESP: 02/04383-7
dc.description.sponsorshipIdFAPESP: 04/00217-0
unesp.campusUniversidade Estadual Paulista (UNESP), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt
Localize o texto completo

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record