Flavopiridol as cyclin dependent kinase (CDK) inhibitor: a review

Abstract

Flavopiridol (alvocidib) is a synthetic flavonoid based on the extract from an Indian plant developed for potential treatment of cancer whose first clinical trials were initiated in 1994 as a frontline combination therapy for leukaemia. It is a potent Cyclin Dependent Kinase (CDK) inhibitor with preferential activity against CDK9. Several phase I and II trials using flavopiridol as a single agent and in combination with standard chemotherapeutic regimens and various tumor types are ongoing. Moreover, the combination of flavopiridol with gemcitabine, imatinib mesylate, SN-38 (the active metabolite of CPT-11) and doxorubicin show synergistic therapeutic effect in inducing mortality of cancer cells. Present study enlightens the individual and combined therapeutic and toxic profiles of flavopiridol. The synthesis, mechanism of action, preclinical and clinical outcomes of flavopiridol till date have been discussed in the current study.