Rottlerin, a Novel Protein Kinase Inhibitor

Rottlerin, a compound from Mallotus philippinensis, is shown to inhibit protein kinases with some specificity for PKC. To some extent, the novel inhibitor is able to differentiate between PKC isoenzymes, with IC50 values for PKCδ of 3-6 μM, PKCα,β,γ of 30-42 μM and PKCϵ,η,ζ of 80-100 μM. Inhibition of PKC appears, at least in part, to be due to a competition between rottlerin and ATP. Among the protein kinases tested, only CaM-kinase III is suppressed by rottlerin as effectively as PKCδ. The chemical structure of rottlerin might serve as a basis for the development of novel inhibitors with improved selectivity for a distinct PKC isoenzyme, such as PKCδ, or for CaM-kinase III.