Protein kinase C, an elusive therapeutic target?

Nat Rev Drug Discov. 2012 Dec;11(12):937-57. doi: 10.1038/nrd3871.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / etiology
  • Clinical Trials as Topic
  • Diabetes Complications / drug therapy
  • Enzyme Activation
  • Heart Diseases / drug therapy
  • Heart Diseases / etiology
  • Humans
  • Isoenzymes / physiology
  • Neoplasms / drug therapy
  • Neoplasms / etiology
  • Organ Transplantation
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / chemistry
  • Protein Kinase C / physiology
  • Protein Kinase Inhibitors / therapeutic use*


  • Isoenzymes
  • Protein Kinase Inhibitors
  • Protein Kinase C