Myoferlin (MYOF)蛋白与癌症的恶性程度和患者的低生存期密切相关，在肿瘤转移过程中发挥着关键作用。因此发现MYOF小分子抑制剂，详细评价其抑制肿瘤转移和复发能力及阐述具体的分子作用机制，对于抗肿瘤转移药物发现具有非常重要的意义。但前期深入研究受限于无MYOF小分子抑制剂，我们课题组从基于优势结构的抗肿瘤先导化合物优化出发，通过分子探针等技术手段，近期首次报道了靶向MYOF的小分子抑制剂WJ460。但后续的研究证实WJ460本身还存在一些不足，因此，本项目旨在通过关键模块替换等一系列策略，在WJ460研究结果的基础上对其进行合理设计和系统结构优化，解决WJ460结合活性和代谢稳定性不高的问题，发展体外结合活性更加特异、体内活性更高和成药性更好的靶向MYOF新型抗肿瘤化学分子实体，为候选药物的系统临床前研究奠定坚实基础，以期突破MYOF靶点尚无候选药物报道的现状。

Myoferlin (MYOF) protein plays pivotal role in tumor metastasis, and which is closely correlated with the malignant degree of cancer and the low survival time. Thus, it is great significance to discovery of MYOF inhibitors for the development of novel antitumor metastasis drugs and detailed evaluation of its effect against tumor metastasis and recurrence as well as elaboration of its specific molecular mechanisms. However, the previous in-depth research is limited since the lack of small molecular inhibitors of MYOF. Based on structural optimization of antitumor lead compounds which were focused on the privileged structures, our research group recently reported WJ460 as a first small molecular inhibitor targeting MYOF through the design and synthesis of probe molecules as well as other techniques. But subsequent research confirmed that WJ460 itself still has several shortcomings. Therefore, the project aims to solve the problems of low binding activity and metabolic stability of WJ460 through reasonable design and systematic structure optimization on the basis of previous results of WJ460 via key scaffold replacement as well as other strategies. And developing novel chemical molecular entity targeting MYOF with more specific binding activities in vitro, higher activities in vivo and better drug-like properties. It lays a solid foundation for the systematic preclinical study of candidate drugs in order to break through the status quo of no drug candidate targeting MYOF.