title: Protein kinase C, an elusive therapeutic target?
abstract: Protein kinase C (PKC) has been a tantalizing target for drug discovery ever since it was first identified as the receptor for the tumour promoter phorbol ester in 1982. Although initial therapeutic efforts focused on cancer, additional indications--including diabetic complications, heart failure, myocardial infarction, pain and bipolar disorder--were targeted as researchers developed a better understanding of the roles of eight conventional and novel PKC isozymes in health and disease. Unfortunately, both academic and pharmaceutical efforts have yet to result in the approval of a single new drug that specifically targets PKC. Why does PKC remain an elusive drug target? This Review provides a short account of some of the efforts, challenges and opportunities in developing PKC modulators to address unmet clinical needs.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305-5174, USA. mochly@stanford.edu
authors.forename: Daria
authors.initials: D
authors.lastname: Mochly-Rosen
authors.forename: Kanad
authors.initials: K
authors.lastname: Das
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Grimes
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy / Q000209:etiology; D002986:Clinical Trials as Topic; D048909:Diabetes Complications / Q000188:drug therapy; D004789:Enzyme Activation; D006331:Heart Diseases / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology; D016377:Organ Transplantation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C