title: 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.affiliation: Tokai University, Bohseidai, Ishehara, Kanagawa, Japan. yonet2301@yahoo.co.jp
authors.forename: Tomo
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Riho
authors.initials: R
authors.lastname: Kurata
authors.forename: Minoru
authors.initials: M
authors.lastname: Kimura
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D018390:Gene Targeting; D006801:Humans; D010330:Patents as Topic; D010455:Peptides / Q000627:therapeutic use*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; C527142:KAI 9803; C584124:KAI-1678; D010455:Peptides; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon