T. N.T. Nguyen and J. J. Tepe Pages 4368 - 4374 ( 7 )
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.
Checkpoint kinase 2,chemotherapy,kinase inhibitors,DNA,DNA-damage,ionizing radiation,chemotherapeutic agents,cancer,serine/threonine protein,biological activity
, Department of Chemistry, College of Natural Sciences, Michigan State University, East Lansing, MI, 48824, USA.