title: Current inhibitors of checkpoint kinase 2.
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.
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: T N T
authors.initials: TN
authors.lastname: Nguyen
authors.forename: J J
authors.initials: JJ
authors.lastname: Tepe
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases