p53是存在人體細胞內的一種抗癌蛋白質，它有抑制細胞生長及維持遺傳物質完整性的功能。而轉?因子 NF-κB 則為相反，在許多癌症患者身上發現有NF-κB被活化的現象。近??有?多的研究皆個別針對 p53 或 NF-κB 為標靶做藥物設計。事實上研究發現，p53 及 NF-κB 這?個訊息傳遞?徑是有很密?的關係，因此在藥物設計上，?能設計出一種化合物，能同時活化 p38 蛋白及抑制轉?因子 NF-κB，必能成為一強效藥劑。這篇研究計畫的目的即為?用?種?同的 approach，一為 modify 已知有雙重功能的天然物，一為設計能調控?個?徑的共同 nodal point 的化合物，期望?用這?種設計原?，能發展出新型能同時活化p38 蛋白及抑制轉?因子 NF-κB的小分子抗癌藥物。 Both DNA binding transcription factor p53 and NF-κB play important roles in human cancer. Inactivation of p53 and hyperactivation of NF-κB is often detected in cancer patients. Efforts have so far been made designing agents that inhibit /activate these pathways selectively. Since these pathways are related in some ways, it would be logical to search for an agent that has dual function. In this research proposal, we attempt to design such an agent from two approaches: one is to modify a compound that was known to possess such dual activity (in this case would be the sesquiterpene lactones) and alternatively, we can also find a common point between these two pathways (such as AKT) and modulate it accordingly. We hope by attacking two targets with just one drug, a much more potent anticancer agent can be developed.
