宫颈癌居发展中国家女性癌症致死率的第二位，目前尚缺乏特异性靶向治疗手段，亟需新靶标和新药物的发现研究。血根碱对宫颈癌等多种肿瘤具有抗增殖作用，但存在活性弱、选择性差、代谢不稳定等缺陷。在前期探索性研究中，我们通过对血根碱进行结构改造和活性筛选，发现其类似物JND3688能够选择性抑制宫颈癌细胞Hela的增殖（IC50=44.23±0.31nM），而对H1975、H1299等其他40余种肿瘤细胞的活性较弱（多数细胞的IC50大于10μM）。初步作用机制研究发现，JND3688抗宫颈癌细胞作用机制可能与C-MYC及P70蛋白有关。本项目拟以JND3688为先导化合物，进行系统的构效关系研究，以发现活性、选择性、代谢性质更优的分子；同时结合活性导向的蛋白谱分析（ABPP）等技术进行靶标发现和验证研究，以期为靶向抗宫颈癌药物研究奠定基础。

Cervical cancer is the second common cause of cancer death in developing countries. It is an urgent need to discover novel targets and drugs for cervical cancer therapy because there are still no specific target drugs for it. Sanguinarine display anti-tumor effects against multiple cancers including cervical cancer, but it possess some bad pharmacological defects, including weak activity, poor selectivity and unstable metabolism. In early exploratory study, we performed structure modification of Sanguinarine and activities screen of its derivatives. We found JND3688, a sanguinarine analogue, could selectively inhibit the proliferation of cervical cancer cells Hela, with an IC50 of 44.23±0.31nM, but weakly inhibit H1975,H1299 and other 40 kinds of tumor cells, with the IC50 of most cells > 10μM. Through preliminary mechanism study, we found the proteins of C-MYC and P70 may be related to the selective anti-cervical action of JND3688. This project intends to take JND3688 as the lead compound to systematically investigate the structure-activity relationship in order to discover molecules with better activation, selectivity and metabolism properties. We also discover and validate the target of JND3688 analogues using the affinity-based proteome profiling (ABPP) and other techniques. This project will lay a foundation for the development of targeted drugs for cervical cancer.