MicroRNA-21是一种致癌基因，抑制MicroRNA-21的表达或活性可抑制肿瘤的生长。MicroRNA-21抑制剂可能是下一个抗肿瘤药物研发的热点。本项目以我们发现的MicroRNA-21小分子抑制剂1j为先导化合物，采用合理药物设计法，将化合物1j的不同位置关环，设计出多种类型的化合物；合成、表征设计的化合物；采用实时定量PCR技术研究化合物抑制MicroRNA-21在Hela细胞中的活性，总结构效关系；采用光亲和标记技术研究高活性化合物的作用靶点和作用位点；采用MTT法评价化合物抑制人肿瘤细胞增值的活性；采用人肿瘤裸鼠移植瘤模型考察化合物的体内抗肿瘤活性。通过本项目的研究，可发现结构新颖、活性高的MicroRNA-21小分子抑制剂，并阐明其构效关系和作用靶点。同时，可推动MicroRNA-21抑制剂的研究，发现具有自主知识产权的抗肿瘤药物。既有理论意义，又有潜在的研发前景。

MicroRNA-21 is an oncogene. Inhibiting the expression or activity of MicroRNA-21 can inhibit tumor growth. MicroRNA-21 inhibitors could be next hot spots to developmental anti-tumor drugs. In this project, compound 1j, discovered by our group, is used as a lead compounds. We shall adopt rational drug design method to design the novel types of MicroRNA-21 small molecule inhibitors by ring closure of different position compound 1j. The designed new compounds will be synthesized and characterized. The activity of synthesized compounds inhibiting MicroRNA-21 in Hela cell line will be evaluated by real time quantitative PCR technology. The structure activity relationship of tested compounds will be revealed. The active compound target will be elucidated by photoaffinity labeling technology. The antiproliferative activity of synthesized compounds will be determined by MTT method. The antitumor effects of compounds in vivo will be investigated with nude mice transplantation tumor model. The study of project can discover novel structure, high active MicroRNA-21 small molecule inhibitors, and disclose the structure-activity relationship and the target of active compound. Meanwhile, the study of project can promote the research on MicroRNA-21 inhibitor, discover the antitumor drugs with independent intellectual property. There are both theoretical significance and development prospects of a new antitumor drug to carry out the project.