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

在这项研究赠款中，我们打算在分子水平上确定蛋白激酶C（PKC）的激活机制，该机制是根据有效的异苯并胡拉诺酮（IB）衍生物设计的，用于PKC。IB衍生物显示了PKC的激活或抑制，依赖于其替代品。此外，本研究的主要主题是澄清PKC抑制剂IB-15 A的抑制机制，对PKC激活剂的分析也是必要的。在这三年里，我们首次揭示了PKC激活器的几个特性。然后我们找到了一个潜在的PKC抑制剂IB-15 A showed inhibition of PKC·by probally through the distinct binding site from that of the typical PKC activator and by disturbing the interaction of PKC with lipid.

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.