肝癌在我国是一种高发肿瘤，从海洋微生物中寻找抗肝癌的候选药物具有重大临床意义 。WB是本课题组从海洋微生物中分离的新化合物，前期研究证明其在体内外有针对性的抗肝癌作用且毒副作用低，基本完成了化合物的大规模发酵制备及候选药物的临床前研究 ，成药前景良好。分子作用机制研究表明其能激活Ras蛋白，导致P53升高从而引起肝癌细胞的 凋亡和周期阻滞。本课题拟进一步研究WB对RASAL1和SOS活性的影响，明确其激活Ras的分子途 径，利用计算机模拟分子对接技术-基于多靶点反向分子对接的药物筛选技术（INVDOCK）、药 物亲和反应靶标稳定技术（DARTS）、多模式毛细管电泳技术等明确其直接作用靶蛋白，通过 干扰RNA、抑制剂等技术研究信号通路中信号分子的变化明确Ras蛋白激活P53的具体信号通路 。通过本研究，阐明WB的直接分子靶点及抗肝癌的分子作用途径，为抗肝癌药物研究提供新的作用靶点和候选药物。

Hepatocellular carcinoma is a high incidence of tumors in Chinese population and discovary anti-hepatoma drug candidate from marine microorganisms has important clinical significance.WB is new compounds isolated from marine microorganisms and preliminary studies prove the anti-hepatoma effecte in vivo and in vitro, and high efficacy, but low toxic and side effect. The preclinical studies was completedand and shown the good pharmaceutical prospect. The molecular mechanism studies have shown that it can activate Ras, lead to elevated p53 and cause liver cancer cell cycle arrest and apoptosis. This study intends to further clarify the molecular pathways of activation of Ras and directly target protein for WB,.Through this study, to elucidate the direct molecular target of WB and the molecular mechanism of anti-liver cancer . To provide new targets for the study of anti-hepatoma drugs.