PKC delta and epsilon in drug targeting and therapeutics.

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.

• Authors: Tomo Yonezawa, Riho Kurata, Minoru Kimura, Hidetoshi Inoko
• Journal: Recent patents on DNA & gene sequences (Recent Pat DNA Gene Seq) Vol. 3 Issue 2 Pg. 96-101 ( 2009) ISSN: 2212-3431 [Electronic] United Arab Emirates
• PMID: 19519579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

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

Topics

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