PROTAC（Proteolysis-Targeting Chimera）技术是近年兴起的一种新型药物研发方向。该技术通过应用小分子化合物招募细胞中的E3泛素连接酶，利用自身的泛素-蛋白酶体系统实现对靶向特定蛋白的降解。理论上，只需要小分子药物短暂地与致癌蛋白结合，给致癌蛋白打上“泛素化”的标签就可以实现高效特异性的蛋白降解。这些小分子药物不需要很高的浓度，可以循环使用，并且蛋白被降解后需要重新合成才能恢复功能，这就可能推迟了抗药性的产生。

代表性论文：

1. L. Wang, X. Shao, T. Zhong, Y. Wu, A. Xu, X. Sun, H. Gao, Y. Liu, T. Lan, Y. Tong, X. Tao, W. Du, W. Wang, Y. Chen, T. Li, X. Meng, H. Deng, B. Yang, Q. He, M. Ying*, Y. Rao*, 'Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy',  Nature Chemical Biology , 2021, 16, 567-575.

2. S. Su, Z. Y, H. Gao, H. Yang, S. Zhu, Z. An, J. Wang, Q. Li, S. Chandarlapaty, H. Deng, W. Wu*, Y. Rao*, Potent and Preferential Degradation of CDK6 via PROteolysis TArgeting Chimera Degraders.  Journal of Medicinal Chemistry , 2019, 62,  DOI: 10.1021/acs.jmedchem.9b00871.

3. X. Sun, J. Wang, X. Yao, W. Zheng, Y. Mao, T. Lan, L. Wang, Y. Sun, X. Zhang, Q. Zhao, J. Zhao, R-P. Xiao, X. Zhang*, G. Ji*, Y. Rao*, ‘A Chemical Approach for Global Protein Knockdown from Mice to Non-human Primates’,  Cell Discovery , 2019, DOI: 10.1038/s41421-018-0079-1.

4. Z. An, W. Lv, S. Su, W. Wu*, Y. Rao*, ‘Developing potent PROTACs tools for selective degradation of HDAC6 protein’,  Protein & Cell , 2019, DOI: 10.1007/s13238-018-0602-z.

5. Y. Sun, X. Zhao, N. Ding, H. Gao, Y. Wu, Y. Yang, M. Zhao, J. Hwang, Y. Song, W. Liu *, Y. Rao*, ‘PROTAC-Induced BTK Degradation as a Novel Therapy for Mutated BTK C481S Induced Ibrutinib-Resistant B-Cell Malignancies’,  Cell Research , 2018, 22, 779–781.