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研究员

孙永汇

职 称:助理教授

所属科室:合成药物化学研究室

导师类别:博士生导师

联系方式:sunyonghui@imm.ac.cn

所属重点实验室:天然药物活性物质与功能国家重点实验室;
活性物质适药化北京市重点实验室

个人简介

孙永汇,助理教授,博士生导师。2018年于清华大学药学院获得博士学位,2019-2022年于哈佛大学医学院和清华大学药学院进行博士后研究。曾开发了世界首例突变型BTK PROTAC降解剂,克服了临床一线抗癌药ibrutinib的耐药性和副作用。代表性科研成果在Cell Research、Leukemia、Chemical Science等国际著名期刊发表,曾入选清华大学“水木学者”计划,2022年11月加入药物研究所独立开展研究工作。

研究方向

本课题组致力于探究靶向蛋白质降解技术(proteolysis-targeting chimeras,PROTAC)及分子胶,利用其结合力、靶向性、蛋白全面失活等优势,获得临床相关的抗肿瘤等治疗人类严重疾病的活性分子。解决小分子耐药、副作用及靶点“不可成药”性等关键科学问题。
具体研究方向:
1. 以克服人类严重疾病为导向,开发新型小分子诱导不可成药/耐药靶点的选择性降解。
2. 基于计算机辅助等技术,开发不可成药靶点的新型抑制剂。
3. 开发新型合成手段及新型生物学化学技术。

发表论文

1. Yonghui Sun#, Xingwang Zhao#, Ning Ding#, Hongying Gao#, Yue Wu, Yiqing Yang, Meng Zhao, Jinseok Hwang, Yuqin Song, Wanli Liu*, Yu Rao*. PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies. Cell Research 2018, 28, 779-781.
2. Yonghui Sun#, Ning Ding#, Yuqin Song#, Zimo Yang, Wanli Liu*, Jun Zhu*, Yu Rao*. Degradation of Bruton’s tyrosine kinase mutants by PROTACs for potential treatment of ibrutinib-resistant non-Hodgkin lymphomas. Leukemia 2019, 33, 2105-2110.
3. Yonghui Sun#, Tianyu Sun#, Yundong Wu, Xinhao Zhang*, Yu Rao*. A diversity- oriented synthesis of bioactive benzanilides via a regioselective C(sp2)-H hydroxylation strategy. Chemical Science 2016, 7, 2229-2238.
4. Yonghui Sun, Yu Rao*. Protein Degradation with New Chemical Modalities: Successful Strategies in Drug Discovery and Chemical Biology (Chapter 8). Drug Discovery, Royal Society of Chemistry 2020, ISBN: 978-1-78801-686-5.
5. Zimo Yang#, Yonghui Sun#, Zhihao Ni, Celi Yang, Yan Tong, Yujie Liu, Haitao Li, Yu Rao*. Merging PROTAC and molecular glue for degrading BTK and GSPT1 proteins concurrently. Cell Research 2021, 31, 1315-1318.
6. Yonghui Sun#, Xin Luo#, Zimo Yang, Wenxing Lv, Lixia Chen, Hua Li*, Yu Rao*. Developing potent BTKC481S PROTACs for ibrutinib-resistant malignant lymphoma. Chinese Chemical Letters 2023, 34, 107924.
7. Xinglin Yang#, Yonghui Sun#, Tianyu Sun, Yu Rao*. Auxiliary-assisted palladium-catalyzed halogenation of unactivated C(sp3)-H bonds at room temperature. Chemical Communications 2016, 52, 6423-6426.
8. Xiuyun Sun#, Yonghui Sun#, Chao Zhang, Yu Rao*. Room-temperature Pd-catalyzed C-H chlorination by weak coordination: one-pot synthesis of 2-chlorophenols with excellent regioselectivity. Chemical Communications 2014, 50, 1262-1264.
9. Xiuyun Sun#, Yonghui Sun#, Yu Rao*. Cyclobutanones as useful synthons for the preparation of bioactive molecules and fused-ring chemicals. Current Organic Chemistry 2016, 20, 1878-1901.
10. Xinglin Yang, Yonghui Sun, Zhang Chen, Yu Rao*. A General Approach towards Catechol and Pyrogallol through Ruthenium- and Palladium-Catalyzed C-H Hydroxylation by Weak Coordination. Advanced Synthesis & Catalysis 2014, 356, 1625-1630.
11. Xiuyun Sun, Yonghui Sun, Yu Rao*. A gram-scale synthesis of multi-substituted arenes via palladium catalyzed C-H halogenation. Chinese Chemical Letters 2014, 25, 667-669.
(# co-first author, * corresponding author)

专著

专利

1. Yu Rao, Wanli Liu, Zimo Yang, Yonghui Sun, Zhihao Ni, Can Zhu, Bing Yang, Yu Xinli. Targeted BTK protein degradation compound, its preparation method and application in treating autoimmune disease and tumor. Faming Zhuanli Shenqing, CN 110724143 A 20200124. 2020, Authorized Patent.

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