Protein kinase C intervention: the state of play.
Intervention in protein kinase C (PKC) has a chequered history, partly because of the poor selectivity of many inhibitors and partly a reflection of the sometimes antagonistic action of related PKC isoforms. Recent advances in targeting PKC isoforms have come from structural work on isolated kinase domains that have provided opportunities to drive selectivity through structure-based avenues. The promise of isoform selective inhibitors and the rationale for their development are discussed in the broader context of the PKC inhibitor arsenal.
Roffey
Jon
J
Discovery Laboratory, Cancer Research Technology Limited, Wolfson Institute for Biomedical Research, London, UK.
Rosse
Carine
C
Linch
Mark
M
Hibbert
Andrew
A
McDonald
Neil Q
NQ
Parker
Peter J
PJ
D000818:Animals; D020134:Catalytic Domain; D002986:Clinical Trials as Topic; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D005810:Multigene Family; D009369:Neoplasms / Q000188:drug therapy; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D011493:Protein Kinase C