作为一个天然产物，雷公藤红素在多项药理学研究中展示出了良好的生物活性。但由于其具有较大的毒性，限制了其进入临床研究。雷公藤红素良好的抗肿瘤活性是其备受关注的主要原因，特别是近年来发现其可以很好的抑制热休克蛋白90（HSP90），而成为目前的研究热点。基于此，本项目在前期研究基础上，拟对其C-2，C-3位置进行结构修饰与改造，将所得到的衍生物进行HSP90抑制试验和体外肿瘤细胞增殖抑制测试，并测试其对正常细胞的毒性。对筛选出活性好的化合物进行体内小鼠肿瘤模型试验，并进行作用机制研究。利用计算机辅助药物设计技术，结合活性数据，研究其构效关系，为后续进一步开发基于HSP90抑制的雷公藤红素衍生物提供新的思路和指导。

As a natural compound, celastrol exhibits desirable biology activity in various of pharmacological research. However, it can’t be studies in clinical due to its high toxicity. Celastrol is highly concerned primarily because of its good antitumor activity and it has become a study hotspot due to good inhibition of heat shock protein 90 (HSP90). Based on our previous study, we plan to modify in its C-2 and C-3 position to get the target derivatives, and evaluate their activity using HSP90 kinase inhibition essay and anti-proliferative essay, and their toxicity against human normal cell will also be tested. And then, the derivatives which are ranked on the top of their activity will be chosen to test in vivo antitumor in mouse model and study on their mechanism. What’ more, structure-activity relationship of these derivatives will be studied using computer aided drug design technology combined with activity data, these can provide a new strategy for developing new celastrol derivatives targeted HSP90.