PKC delta and epsilon in drug targeting and therapeutics

Recent Pat DNA Gene Seq. 2009;3(2):96-101. doi: 10.2174/187221509788654205.

Abstract

Protein kinase C (PKC) belongs to the serine and threonine kinase family. At least ten PKC isoforms have been identified and subdivided into three groups: classical (alpha, beta I, beta II and gamma), novel (delta, epsilon, theta and eta), and atypical (zeta and iota/lambda). Two calcium-insensitive isoforms of novel PKC, PKC delta and epsilon, have received particular attention as promising targets for new drugs. PKCs play a multifaceted role in cellular responses in a range of tissues. Professor Mochly-Rosen's group and KAI Pharmaceuticals Inc. have developed drugs targeted against PKC delta (KAI-9803) and epsilon (KAI-1678). These drugs ameliorate pathological conditions in acute myocardial infarction and reduce pain via specific modulation of membrane-translocation of PKC delta or epsilon. Another research group has recently used the KinAce() approach to produce PKC epsilon-abrogating peptides (KCe-12 and KCe-16) that are based on the catalytic domain of PKC. These peptides specifically inhibit PKC epsilon and ameliorate pathological conditions in a rodent insulin resistance model. This review describes the development of these therapeutic drugs targeting PKC delta and epsilon by two independent groups in the light of recent patents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enzyme Inhibitors / therapeutic use*
  • Gene Targeting
  • Humans
  • Patents as Topic*
  • Peptides / therapeutic use*
  • Protein Kinase C-delta* / antagonists & inhibitors
  • Protein Kinase C-delta* / genetics
  • Protein Kinase C-delta* / metabolism
  • Protein Kinase C-epsilon* / antagonists & inhibitors
  • Protein Kinase C-epsilon* / genetics
  • Protein Kinase C-epsilon* / metabolism

Substances

  • Enzyme Inhibitors
  • KAI 9803
  • KAI-1678
  • Peptides
  • Protein Kinase C-delta
  • Protein Kinase C-epsilon