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Current Inhibitors of Checkpoint Kinase 2

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Abstract:

Checkpoint kinase 2 is a serine/threonine protein which functions as an important transducer in apoptosis or DNA repair following activation by DNA damage. Inhibition of checkpoint kinase 2 is thought to sensitize p53-mutated or p53-deficient cancerous cells but protect normal tissue following DNA-damage caused by ionizing radiation or chemotherapeutic agents. The development of checkpoint kinase inhibitors for the treatment of cancer has therefore been a major objective in drug discovery over the past decade. Several inhibitors have been co-crystallized in the active site of checkpoint kinase 2 revealing important features of effective inhibitors. Some of these inhibitors have entered clinical trials in the last decade. This review describes and discusses the most recent inhibitors of checkpoint kinase 2 as reported in the literature, including an evaluation of biological activity.





Keywords: Checkpoint kinase 2; DNA; DNA-damage; biological activity; cancer; chemotherapeutic agents; chemotherapy; ionizing radiation; kinase inhibitors; serine/threonine protein

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986711797200390

Publication date: October 1, 2011

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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