More recently medical chemistry research has been focused on proteins that drive and controlcell cycle progression. Among them, the cyclin dependent kinases (cdk’s) are a group ofserine/threonine kinases, which rule the transition between successive stages of the cell cycle. Theactivity of cdk’s is regulated by multiple mechanisms, including binding to cyclins, which is a broadclass of positive...

more recently medical chemistry research has been focused on proteins that drive and controlcell cycle progression. among them, the cyclin dependent kinases (cdk’s) are a group ofserine/threonine kinases, which rule the transition between successive stages of the cell cycle. theactivity of cdk’s is regulated by multiple mechanisms, including binding to cyclins, which is a broadclass of positive...

Flavopiridol, a cyclin-dependent kinase (cdk) inhibitor, can cause cell cycle arrest, induce apoptosis in cancer cells, and inhibit tumor cell growth in vivo. The present study investigated the in vitro radiosensitizing effect of flavopiridol and the underlying molecular mechanisms in a murine ovarian cancer cell line, OCA-I. Flavopiridol inhibited cell growth in a dose-dependent manner and enh...

Flavopiridol, the first potent cyclin-dependent kinase inhibitor to enter clinical trials, was recently found to be cytotoxic to noncycling cells. The present studies were performed to examine the hypothesis that flavopiridol, like several other antineoplastic agents that kill noncycling cells, might also interact with DNA. Consistent with this possibility, treatment of A549 human lung cancer c...

The present studies have determined whether interactions between the cyclin-dependent kinase inhibitor flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat; Zolinza) occur in breast cancer cells. MDA-MB-231 and MCF7 cells were treated with flavopiridol (25-100 nmol/L) and vorinostat (125-500 nmol/L) in vitro, and mechanisms of cell killing were de...

Flavopiridol, the first potent cyclin-dependent kinase inhibitor to undergo clinical trials as an antineoplastic agent in the United States, has attracted considerable attention because of its unique cellular targets and its ability to kill noncycling tumor cells in vitro. To better understand how flavopiridol might be used clinically, the present study used colony-forming assays to examine the...

PURPOSE Flavopiridol is a cyclin-dependent kinase inhibitor currently under development by the National Cancer Institute both as a single agent and in combination with chemotherapy. There have been numerous reports that flavopiridol potently enhances the induction of apoptosis by chemotherapy. However, the effect of flavopiridol on radiotherapy (RT)-induced apoptosis has been largely untested. ...

Flavopiridol, a cyclin-dependent kinase inhibitor currently undergoing clinical evaluation, has a dose-limiting toxicity of diarrhea. Preclinical data on flavopiridol metabolism indicate that flavopiridol undergoes hepatic glucuronidation. The purpose of this study is to evaluate whether the occurrence of diarrhea is related to the systemic glucuronidation of flavopiridol. Parent drug and metab...

Flavopiridol treatment can lead to apoptosis via a mechanism that has been associated with down-regulation of Mcl-1. Likewise, recent studies from our laboratory demonstrated that E2F1 leads to transcriptional repression of Mcl-1 and subsequently apoptosis. Given the ability of cyclin/cyclin-dependent kinase 2 antagonists to kill transformed cells, we surmised that flavopiridol may stabilize E2...