CDK inhibitors in clinical development for the treatment of cancer.

Abstract:

:Cyclin-dependent protein kinases (CDKs) are key regulators of the cell division cycle, whose various checkpoints proliferating cells must traverse. Since CDK deregulation, either through direct or indirect means, is found in most cancer cells, pharmacological CDK inhibition has become an attractive strategy towards mechanism-based and non-genotoxic therapies in oncology. Over the last decade, discovery and lead optimisation efforts have provided a wealth of potential drug candidate molecules capable of inhibiting CDKs, blocking cell-cycle progression, modulating transcription and inducing apoptosis selectively in cancer cells. However, only few such agents have as yet reached clinical evaluation. Here, the preclinical and clinical results obtained so far with flavopiridol (L868275, HMR1275; Aventis), 7-hydroxystaurosporine (UCN-01, KW-2401; Kyowa Hakko Kogyo) and roscovitine (R-roscovitine, CYC202; Cyclacel) are summarised. Furthermore, the potential for monotherapy and applications in combination with existing drugs are discussed.

authors

Fischer PM,Gianella-Borradori A

doi

10.1517/13543784.12.6.955

subject

Has Abstract

pub_date

2003-06-01 00:00:00

pages

955-70

issue

6

eissn

1354-3784

issn

1744-7658

journal_volume

12

pub_type

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