Clarification research for molecular mechanism of a novel type of protein kinase C inhibitor

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In this research grant, we intended to clarify the activation mechanism of protein kinase C(PKC) at molecular level by utilizing isobenzofuranone(IB) derivatives, which were designed based on the physiological activators, diacylglycerols(DAG), for PKC. IB derivatives showed either activation or inhibition of PKC・depended on their substituents. Although the main subject of this research was clarification of the inhibition mechanism of PKC inhibitor IB-15A, analysis of the PKC activators was also necessary. In these three years, we first revealed the features of several PKC activators. And then we found that a potent PKC inhibitor IB-15A showed inhibition of PKC・by probably through the distinct binding site from that of the typical PKC activator and by disturbing the interaction of PKC with lipid.