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  • Title: Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol.
    Author: de Azevedo WF, Canduri F, da Silveira NJ.
    Journal: Biochem Biophys Res Commun; 2002 Apr 26; 293(1):566-71. PubMed ID: 12054639.
    Abstract:
    Flavopiridol has been shown to potently inhibit CDK1 and 2 (cyclin-dependent kinases 1 and 2) and most recently it has been found that it also inhibits CDK9. The complex CDK9-cyclin T1 controls the elongation phase of transcription by RNA polymerase II. The present work describes a molecular model for the binary complex CDK9-flavopiridol. This structural model indicates that the inhibitor strongly binds to the ATP-binding pocket of CDK9 and the structural comparison of the complex CDK2-flavopiridol correlates the structural differences with differences in inhibition of these CDKs by flavopiridol. This structure opens the possibility of testing new inhibitor families, in addition to new substituents for the already known leading structures such as flavones and adenine derivatives.
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