Protein kinase C inhibitors as novel anticancer drugs
- 1 December 2001
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 10 (12), 2117-2140
- https://doi.org/10.1517/13543784.10.12.2117
Abstract
The role of PKC isoforms in signal transduction pathways involved in regulation of the cell cycle, apoptosis, angiogenesis, differentiation, invasiveness, senescence and drug efflux are reviewed, along with the clinical results on the current crop of PKC inhibitors, including midostaurin (PKC-412, CGP 41251, N-benzoylstaurosporine), UCN-01 (7-hydroxystaurosporine), bryostatin 1, perifosine, ilmofosine, Ro 31-8220, Ro 32-0432, GO 6976, ISIS-3521 (CGP 64128A) and the macrocyclic bis (indolyl) maleimides (LY-333531, LY-379196, LY-317615). An appreciation of the complex, often contradictory roles of PKC isoforms in signal transduction pathways involved in cancer is important for interpreting the clinical results observed with PKC inhibitors of varying selectivity. An antisense oligonucleotide, ISIS-3521 and two orally available small molecule inhibitors, LY 333531 and midostaurin, have now advanced to latter stage development for cancer and/or other indications. These compounds have varying levels of selectiv...Keywords
This publication has 107 references indexed in Scilit:
- Subtype-Specific Translocation of the δ Subtype of Protein Kinase C and Its Activation by Tyrosine Phosphorylation Induced by Ceramide in HeLa CellsMolecular and Cellular Biology, 2001
- Differential Sensitivity of Breast Cancer Cells to Tumor Necrosis Factor-α: Involvement of Protein Kinase CBiochemical and Biophysical Research Communications, 2001
- Specificity and mechanism of action of some commonly used protein kinase inhibitorsBiochemical Journal, 2000
- Advanced Glycation End Product-Induced Peroxisome Proliferator-Activated Receptor γ Gene Expression in the Cultured Mesangial CellsBiochemical and Biophysical Research Communications, 1999
- Apoptosis is induced in glioma cells by antisense oligonucleotides to protein kinase Cα and is enhanced by cycloheximideNeuroReport, 1998
- Bryostatin 1 Induces Biphasic Activation of Protein Kinase D in Intact CellsPublished by Elsevier BV ,1997
- Regulation of p53 by protein kinase C during multi-stage carcinogenesisZeitschrift für Krebsforschung und Klinische Onkologie, 1997
- D-21266, a new heterocyclic alkylphospholipid with antitumour activityEuropean Journal Of Cancer, 1997
- Differential inhibition of cytosolic and membrane‐derived protein kinase C activity by staurosporine and other kinase inhibitorsFEBS Letters, 1995
- Involvement of protein kinase C-ɛ in glucocorticoid-induced apoptosis in thymocytesInternational Immunology, 1994