导师介绍
云彩红 教授
个人简介
云彩红，教授，2004年毕业于中国科学院生物物理研究所，获博士学位。原哈佛大学医学院研究科学家，现任北京大学基础医学院教授、博士导师、北京大学医药卫生分析中心冷冻电镜平台主任。主要从事结构生物学、结构药理学研究和基于三维结构的新药研发，已在Nature、Cell、Cancer Cell、Sci Transl Med、Angew Chem Int Ed等学术期刊上发表近四十篇责任作者论文。阐明表皮生长因子受体（EGFR）突变导致非小细胞肺癌发病或耐药的分子机理（Cell 2016等），是抗 EGFR耐药性突变的首个第三代抑制剂WZ4002（Nature 2009）和首个第四代抑制剂EAI045（Nature 2016）研发工作的核心贡献者之一，所主持研发的 EGFR 第四代备选新药H002已在中、美两国进入临床试验。
联系方式
北京大学基础医学院生物物理学系
E-mail: yunch@hsc.pku.edu.cn
研究方向
结构生物学研究、结构药理学研究、理性和智能的药物设计。
（1）生物大分子机器的结构与功能关系研究
（2）肿瘤发生及药物敏感性的分子机理研究
（3）基于三维结构的药物发现（结构药理学、计算化学与人工智能）
学习与工作经历
2013.10-2019.03，北京大学基础医学院生物物理学系常务副主任
2011.10-今，北京大学基础医学院教授、博士导师
2010.07-2011.10，哈佛大学医学院，研究科学家
2004.11-2010.06，哈佛大学医学院，博士后
1998.09-2004.06， 中国科学院生物物理研究所，获博士学位
授课课程
《结构生物学研究技术》
科研团队
教工：孔璐璐(主管技师)，陈丹丹(主管技师)，韩蕊（博士后）
学生：史超，南凤尾，罗茜，陆尧，许庆勃，李明轩
科研成果
基金项目：
1. 复合物结构研究指导抗肺癌EGFRT790M突变新药研发，国家自然科学基金面上项目，31270769，2013-01至2016-12，80万元，已结题，主持。
2. 蛋白质生命周期过程及调控的分子机制(课题二:蛋白质翻译后修饰的结构生物学研究)，科技部“国家重大科学研究计划(973计划)”，2012CB917202, 2012-01至2016-08，115万元，已结题，课题负责人。
3. 教育部“新世纪优秀人才支持计划”，NCET-12-0013，结构生物学，2013-01至2015-12，50万元已结题，主持。
4. NRDE2及其复合物的结构与功能研究，国家自然科学基金面上项目，32071207， 2021-01至 2024-12, 58万元，主持。
5. 多聚腺苷化修饰RNA的降解机制研究，国家自然科学基金面上项目，32471256， 2025-01至 2028-12, 50万元，主持。
代表性论文：
38) Wu Z(#), Liu X(#), Yan XE(#), Wu X(#), Huang W, Li J, Xiu Y, Lv C, Sun C, Wang Z, Xu G, Wu X, Hu Z, Huang H, Huang X, Zhang J(*), Yun CH(*), Li L(*), Deng X(*). Discovery of Potent and Selective Pyrrolo[2,3-d]pyrimidine Derivatives as Fourth-Generation EGFR Inhibitors Targeting Triple Mutations. J Med Chem. 2025 Sep 9. Online ahead of print.
37) Tai Y(#), Kong L(#), Wang Y(#), Zhao D(#), Chen X, Wu Q, Hao J, Wang X, Liu X, Chen D, Li J, Hu Y, Zhang W(*), Yun CH(*), Zhan Q(*). Identification and characterization of Bufalin as a novel EGFR degrader. Cancer Lett. 2025 Jul 28:623:217715.
36) Zhao CR(#), You ZL(#), Chen DD(#), Hang J(#*), Wang ZB, Ji M, Wang LX, Zhao P, Qiao J(*), Yun CH(*), Bai L(*). Structure of a fungal 1,3-β-glucan synthase. Sci Adv. 2023 Sep 15;9(37):eadh7820.
35) Chen DD(#), Wang ZB(#), Wang LX, Zhao P, Yun CH(*), Bai L(*). Structure, catalysis, chitin transport, and selective inhibition of chitin synthase. Nat Commun. 2023 Aug 8;14(1):4776.
34) Chen DD(#), Hao J(#), Shen CH(#), Deng XM, Yun CH(*). Atomic resolution Cryo-EM structure of human proteasome activator PA28γ. Int J Biol Macromol. 2022 Aug 4;219:500-507.
33) Lu Y(#), Fan Z(#), Zhu SJ(#), Huang X(#), Zhuang Z(#), Li Y, Deng Z, Gao L, Hong X, Zhang T, Li L, Sun X, Huang W, Zhang J, Liu Y, Zhang B, Jiang J, Gui F, Wang Z, Li Q, Song S, Huang X, Wu Q, Chen L, Zhou D, Zhang J, Yun CH(*), Chen L(*), Deng X(*). A new ALK inhibitor overcomes resistance to first- and second-generation inhibitors in NSCLC. EMBO Mol Med. 2022 Jan 11;14(1):e14296.
32) Li S(#), Zhang T(#), Zhu SJ(#), Lei C, Lai M, Peng L, Tong L, Pang Z, Lu X, Ding J, Ren X(*), Yun CH(*), Xie H(*), Ding K(*). Optimization of Brigatinib as New Wild-Type Sparing Inhibitors of EGFRT790M/C797S Mutants. ACS Med Chem Lett. 2022 Jan 7;13(2):196-202.
31) Sun FH(#), Zhao P(#), Zhang N, Kong LL, Wong CCL, Yun CH(*). HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones. Nat Commun. 2021 Feb 15;12(1):1028.
30) Yan XE(#), Ayaz P(#), Zhu SJ(#), Zhao P(#), Liang L, Zhang CH, Wu YC, Li JL, Choi HG, Huang X, Shan Y(*), Shaw DE(*), Yun CH(*). Structural Basis of AZD9291 Selectivity for EGFR T790M. J Med Chem. 2020 Aug 13;63(15):8502-8511.
29) Yang J(#), Shibu MA(#), Kong L(#), Luo J, BadrealamKhan F, Huang Y, Tu ZC, Yun CH(*), Huang CY(*), Ding K(*), Lu X(*). Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors. J Med Chem. 2020 Mar 12;63(5):2114-2130.
28) Shen J(#), Zhang T(#), Zhu SJ(#), Sun M, Tong L, Lai M, Zhang R, Xu W, Wu R, Ding J, Yun CH(*), Xie H(*), Lu X(*), Ding K(*). Structure-Based Design of 5-Methylpyrimidopyridone Derivatives as New Wild-Type Sparing Inhibitors of Epidermal Growth Factor Receptor Triple Mutant (EGFRL858R/T790M/C797S). J Med Chem. 2019 Aug 8; 62(15): 7302-7308.
27) He JB(#), Zhao P(#), Hu ZM, Liu S, Kuang Y, Zhang M, Li B, Yun CH(*), Qiao X(*), Ye M(*). Molecular Characterization and Structural Basis of a Promiscuous C-Glycosyltransferase from Trollius chinensis. Angew Chem Int Ed Engl. 2019 Aug 12;58(33):11513-11520.
26) Wang J(#), Chen J(#), Wu G(#), Zhang H(#), Chen S(#), Du X, Zhang L, Wang K, Fan J, Gao S, Wu X, Zhang S, Kuai B, Zhao P, Chi B, Wang L, Li G, Wong CCL, Zhou Y, Li J(*), Yun CH(*), Cheng H(*). NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction. Genes Dev. 2019 May 1;33(9-10):536-549.
25) Lu X(#), Zhang T(#), Zhu SJ(#), Xun Q, Tong L, Hu X, Li Y, Chan S, Su Y, Sun Y, Chen Y, Ding J, Yun CH(*), Xie H(*), and Ding K(*), Discovery of JND3229 as a New EGFRC797S Mutant Inhibitor with In Vivo Mono-drug Efficacy, ACS Med Chem Lett, 2018 Oct 8;9(11):1123-1127.
24) Ma R(#), Yun CH(*). Crystal structures of pan-IDH inhibitor AG-881 in complex with mutant human IDH1 and IDH2. Biochem Biophys Res Commun. 2018 Sep 18;503(4):2912-2917.
23) Zhao P(#), Yao MY, Zhu SJ, Chen JY, Yun CH(*). Crystal structure of EGFR T790M/C797S/V948R in complex with EAI045. Biochem Biophys Res Commun. 2018 Jul 20;502(3):332-337.
22) Wang Q(#), Liu F(#), Qi S(#), Qi Z(#), Yan XE(#), Wang B, Wang A, Wang W, Chen C, Liu X, Jiang Z, Hu Z, Wang L, Wang W, Ren T, Zhang S, Yun CH(*), Liu Q(*), Liu J(*). Discovery of 4-((N-(2-(dimethylamino)ethyl)acrylamido)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide (CHMFL-PDGFR-159) as a highly selective type II PDGFRα kinase inhibitor for PDGFRα driving chronic eosinophilic leukemia. Eur J Med Chem. 2018 Apr 25;150:366-384.
21) Zhu SJ(#), Zhao P(#), Yang J, Ma R, Yan XE, Yang SY, Yang JW, Yun CH(*), Structural Insights into Drug Development Strategy Targeting EGFR T790M/C797S, Oncotarget, 2018 Jan 10;9(17):13652-13665.
20) Song C(#), Liang L(#), Jin Y, Li Y, Liu Y, Guo L, Wu C, Yun CH(*), and Yin Y(*), RCC2 is a novel p53 target in suppressing metastasis, Oncogene, 2018 Jan 4;37(1):8-17.
19) Yan XE(#), Zhu SJ(#), Liang L, Zhao P, Choi HG, Yun CH(*), Structural basis of mutant-selectivity and drug-resistance related to CO-1686, Oncotarget, 2017 Jun 21;8(32):53508-53517.
18) Chang Y(#), Lu X(#), Shibu MA(#), Dai YB(#), Luo J, Zhang Y, Li Y, Zhao P, Zhang Z, Xu Y, Tu ZC, Zhang Q, Yun CH(*), Huang CY(*), Ding K(*), Structure-Based Design of N-(3-((1H-pyrazolo[3, 4-b]pyridin-5-yl)ethynyl) Benzenesulfonamides as Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors, J Med Chem. 2017 Jul 13;60(13):5927-5932.
17) Kong LL(#), Ma R, Yao MY, Yan XE, Zhu SJ, Zhao P, Yun CH(*), Structural pharmacological studies on EGFR T790M/C797S, Biochem Biophys Res Commun, 2017 Jun 24; 488(2):266-272.
16) Hu C(#), Wang A(#), Wu H(#), Qi Z(#), Li X(#), Yan XE(#), Chen C, Yu K, Zou F, Wang W, Wang W, Wu J, Liu J, Wang B, Wang L, Ren T, Zhang S, Yun CH(*), Liu J(*), Liu Q(*). Discovery and characterization of a novel irreversible EGFR mutants selective and potent kinase inhibitor CHMFL-EGFR-26 with a distinct binding mode. Oncotarget. 2017 Mar 14;8(11):18359-18372.
15) Liang Q(#), Chen Y(#), Yu K(#), Chen C(#), Zhang S(#), Wang A, Wang W, Wu H, Liu X, Wang B, Wang L, Hu Z, Wang W, Ren T, Zhang S, Liu Q, Yun CH(*), Liu J(*). Discovery of N-(3-(5-((3-acrylamido-4-(morpholine-4-carbonyl)phenyl)amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4-(tert-butyl)benzamide (CHMFL-BTK-01) as a highly selective irreversible Bruton's tyrosine kinase (BTK) inhibitor. Eur J Med Chem. 2017 May 5;131:107-125.
14) Wang A(#), Li X(#), Wu H(#), Zou F(#), Yan XE(#), Chen C, Hu C, Yu K, Wang W, Zhao P, Wu J, Qi Z, Wang W, Wang B, Wang L, Ren T, Zhang S, Yun CH(*), Liu J(*), Liu Q(*). Discovery of (R)-1-(3-(4-Amino-3-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (CHMFL-EGFR-202) as a Novel Irreversible EGFR Mutant Kinase Inhibitor with a Distinct Binding Mode. J Med Chem. 2017 Apr 13;60(7):2944-2962.
13) Wang A(#), Yan XE(#), Wu H(#), Wang W(#), Hu C, Chen C, Zhao Z, Zhao P, Li X, Wang L, Wang B, Ye Z, Wang J, Wang C, Zhang W, Gray NS, Weisberg EL, Chen L, Liu J(*), Yun CH(*), Liu Q(*), Ibrutinib Targets mutant-EGFR Kinase With a Distinct Binding Conformation, Oncotarget, 2016 Oct 25;7(43):69760-69769.
12) Chen JY(#), Liu L, Cao CL, Li MJ, Tan K, Yang X and Yun CH(*), Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase, Sci Rep, 2016 Aug 23;6:31425.
11) Fan F(#), He Z(#), Kong LL(#), Chen Q(#), Yuan Q(#), Zhang S, Ye J, Liu H, Sun X, Geng J, Yuan L, Hong L, Xiao C, Zhang W, Sun X, Li Y, Wang P, Huang L, Wu X, Ji Z, Wu Q, Xia NS, Gray NS, Chen L, Yun CH(*), Deng X(*) and Zhou D(*), Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration, Sci Transl Med, 2016 Aug 17;8(352):352ra108.
10) Liang L(#), Yan XE, Yin Y(*) and Yun CH(*), Structural and biochemical studies of PDGFRA kinase domain, Biochem Biophys Res Commun, 2016 Sep 2;477(4):667-72.
9) Liu F(#), Wang B(#), Wang Q(#), Qi Z(#), Chen C(#), Kong LL(#), Chen JY, Liu X, Wang A, Hu C, Wang W, Wang H, Wu F, Ruan Y, Qi S, Liu J, Zou F, Hu Z, Wang W, Wang L, Zhang S, Yun CH(*), Zhai Z(*), Liu J(*), Liu Q(*), Discovery and characterization of a novel potent type II native and mutant BCR-ABL inhibitor (CHMFL-074) for Chronic Myeloid Leukemia (CML), Oncotarget, 2016 Jul 19;7(29):45562-45574.
8) Anastasi S(#), Zhu SJ(#), Ballarò C, Manca S, Lamberti D, Wang LJ, Alemà S, Yun CH(*), Segatto O(*). Lack of Evidence that CYTH2/ARNO Functions as a Direct Intracellular EGFR Activator. Cell. 2016 May 19;165(5):1031-4.
7) Liu L(#), Chen JY(#), Yang B, Wang FH, Wang YH(*), Yun CH(*),Active-State Structures of a Small Heat-Shock Protein Revealed a Molecular Switch for Chaperone Function, Structure, 2015 Nov 3;23(11):2066-75.
6) Yasuda H(#), Park E(#), Yun CH(#), Sng NJ, Lucena-Araujo AR, Yeo WL, Huberman MS, Cohen DW, Nakayama S, Ishioka K, Yamaguchi N, Hanna M, Oxnard GR, Lathan CS, Moran T, Sequist LV, Chaft JE, Riely GJ, Arcila ME, Soo RA, Meyerson M, Eck MJ(*),Kobayashi SS(*), Costa DB(*),Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer, Sci Transl Med, 2013 Dec18;5(216):216ra177.
5) Zhou W(#), Ercan D(#), Chen L(#), Yun CH(#), Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R, Engen JR, Wong KK, Eck MJ, Gray NS(*), Jänne PA(*), Novel mutant-selective EGFR kinase inhibitors against EGFR T790M, Nature, 2009 Dec 24; 462(7276):1070-4.
4) Yun CH(#), Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, and Eck MJ(*), The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP, Proc Natl Acad Sci USA, 2008Feb 12; 105(6):2070-5.
3) Yun CH(#), Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, and Eck MJ(*), Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes: Mechanism of Activation and Insights into Differential Inhibitor Sensitivity, Cancer Cell, 2007 Mar; 11(3):217-27.
2) Yun CH(#), Tang YH, Feng YM, An XM, Chang WR and Liang DC(*), 1.42 Å crystal structure of mini-IGF-1(2): an analysis of the disulfide isomerization property and receptor binding property of IGF-1 based on the three-dimensional structure, Biochem Biophys Res Commun, 2005 Jan 7; 326(1):52-9.
1) Yun CH(#), Bai J, Sun DY, Cui DF, Chang WR and Liang DC(*), Structure of potato calmodulin PCM6: the first report of the three-dimensional structure of a plant calmodulin, Acta Crystallogr D Biol Crystallogr, 2004 Jul; 60(Pt 7):1214-9.