Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anticancer therapies.

ABSTRACT:

Introduction

Checkpoint kinase (CHK) inhibitors offer the promise of enhancing the effectiveness of widely prescribed cancer chemotherapies and radiotherapy by inhibiting the DNA damage response, as well as the potential for single agent efficacy.

Areas covered

This article surveys structural insights into the checkpoint kinases CHK1 and CHK2 that have been exploited to enhance the selectivity and potency of small molecule inhibitors. Furthermore, the authors review the use of mechanistic cellular assays to guide the optimisation of inhibitors. Finally, the authors discuss the status of the current clinical candidates and emerging new clinical contexts for CHK1 and CHK2 inhibitors, including the prospects for single agent efficacy.

Expert opinion

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SUBMITTER: Matthews TP 

PROVIDER: S-EPMC3998639 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature