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dc.contributor.authorCanduri, Fernanda [UNESP]
dc.contributor.authorde Azevedo, Walter Filgueira [UNESP]
dc.date.accessioned2014-05-20T15:27:07Z
dc.date.available2014-05-20T15:27:07Z
dc.date.issued2005-01-01
dc.identifierhttp://dx.doi.org/10.2174/1573409052952233
dc.identifier.citationCurrent Computer-aided Drug Design. Sharjah: Bentham Science Publ Ltd, v. 1, n. 1, p. 53-64, 2005.
dc.identifier.issn1573-4099
dc.identifier.urihttp://hdl.handle.net/11449/37157
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.format.extent53-64
dc.language.isoeng
dc.publisherBentham Science Publ Ltd
dc.relation.ispartofCurrent Computer-aided Drug Design
dc.sourceWeb of Science
dc.subjectCDK2pt
dc.subjectdrug designpt
dc.subjectFlavopiridolpt
dc.subjectRoscovitinept
dc.subjectinhibitorpt
dc.subjectindirubinpt
dc.titleStructural Basis for Interaction of Inhibitors with Cyclin-Dependent Kinase 2en
dc.typeArtigo
dcterms.licensehttp://eurekaselect.com/209
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.identifier.doi10.2174/1573409052952233
dc.identifier.wosWOS:000207958500006
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
dc.relation.ispartofjcr0.770
dc.relation.ispartofsjr0,259
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