Protein kinase C (PKC) represents a family of
phospholipid-dependent
serine/threonine kinase. PKC was detected in almost all types of cells and tissues in the body. The activation of PKC is involved in the signal regulation of many physiological and
pathological processes. PKC has multiple
isoforms (alpha, betaI, betaII, gamma delta, epsilon, eta, theta, xi, iota and micro). PKC-mediated cellular processes are tissue- and
isoform-specific. Investigations on selective or
isoform-specific PKC inhibitors have attracted great attention during last two decades. Recent studies demonstrated that LY333531, a
PKC-beta-specific inhibitor, reduced the development of
diabetic vascular complications in animal models and prevented
hyperglycemia-induced impairment of endothelial-dependent vasodilation in healthy subjects. Results from phase I clinical trial suggested low risk of the inhibitor. Phase III clinical trials on the safety and the preventive effects of the
PKC-beta-specific inhibitor on
diabetic complications are under progress. The efficacy of ISSI-3521, a PKC-alpha antisense inhibitor, on slowing the growth and
metastasis of solid
tumors is currently being examined in clinical trials. Partial responses in the prevention of the progress of
malignancies were found in early phases of clinical trials for
UCN-01 and CGP41251, two partially
isoform-specific PKC inhibitors. Recent findings suggest that
isoform-specific PKC inhibitors are potentially beneficial to the prevention or treatment of some common diseases, including
cancers and
diabetic vascular complications. Safety and efficacy studies of the PKC inhibitors will be required through large-scale long-term clinical trials.