Flavopiridol Hoechst AG.

Article Details

Citation

Zvelebil MJ

Flavopiridol Hoechst AG.

IDrugs. 1998 Jun;1(2):241-6.

PubMed ID
18465538 [ View in PubMed
]
Abstract

Hoechst is developing flavopiridol, a synthetic flavonoid based on an extract from an Indian plant, for the potential treatment of cancer. Flavopiridol, a cyclin-dependent kinase inhibitor, arrests cell division and causes apoptosis in non-small lung cancer cells [283660]. A phase II trial, in collaboration with the National Cancer Institute, has commenced at the University of Chicago Medical Center, which involves patients with high or intermediate-grade lymphoma or multiple myeloma [272937], [277372]. In ex vivo experiments with tumor cells from refractory chronic lymphoblastic leukemia, dose-dependent CDK2 inhibition associated with apoptotic changes was seen at concentrations greater than 100 nM of flavopiridol. In vitro pharmacokinetic studies have shown that flavopiridol undergoes hepatic biotransformation to its corresponding glucoronide by uridine diphosphate glucoronosyltransferases [283791]. Flavopiridol inhibits CDK with an IC50 value of 0.4 mM [285707]. Preclinical toxicology studies in rats and dogs demonstrated dose-related leukopenia and drug-related lesions in the thymus, spleen and bone marrow. The gastrointestinal and bone marrow toxicity was dose-limiting [178579]. Hoechst Marion Roussel expects to launch flavopiridol in the year 2001, with potential sales in excess of DM 750 million [288651].

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AlvocidibCyclin-dependent kinase 2ProteinHumans
Unknown
Inhibitor
Details