Prof. Cai-Hong Yun

CONTACT INFORMATION

E-mail: yunch@hsc.pku.edu.cn

RESEARCH INTERESTS

(1) structure and function of biomacromolecular machines

(2) molecular mechanisms of tumorigenesis and drug sensitivity

(3) drug discovery based on three-dimensional structure (structural pharmacology, computational chemistry and artificial intelligence)

In short

structural biology, structural pharmacology, rational and intelligent drug design

INTRODUCTION

Professor Yun earned his Ph.D. degree from the Institute of Biophysics, Chinese Academy of Sciences, in 2004. He was appointed a research scientist at Harvard Medical School and currently holds positions as a professor at the School of Basic Medical Sciences, Peking University, and Director of the Cryo-Electron Microscopy Facility at the Center for Biomedical Analysis, Peking University. His research focuses on structural biology, structural pharmacology, and structure-based drug design. He has published nearly forty papers as a responsible author in academic journals including  Nature ,  Cell ,  Cancer Cell ,  Sci. Transl. Med. , and  Angew. Chem. Int. Ed . His studies have elucidated the molecular mechanisms underlying the onset of non-small-cell lung cancer (NSCLC) and drug resistance caused by mutations in the epidermal growth factor receptor (EGFR) ( e.g. , Cell 2016, Sci Transl Med 2012). He acted as a major contributor to the successful development of the third-generation inhibitor WZ4002 (Nature 2009) and the fourth-generation inhibitor EAI045 (Nature 2016) that overcome drug-resistant EGFR mutations. The fourth-generation investigational new drug H002, designed to treat EGFR-mutated drug-resistant NSCLC and developed under his direction, has been approved for clinical trials in both China and the United States.

EDUCATION & ACADEMIC APPOINTMENTS

2013.10-2019.03, Deputy Director

Department of Biophysics, School of Basic Medical Sciences, Peking University, Beijing

2011.10-present, Professor

School of Basic Medical Sciences, Peking University, Beijing

2010.07-2011.10, Research Scientist

Harvard Medical School, Boston, MA, USA

2004.11-2010.06, Postdoctoral Research Assistant

Harvard Medical School, Boston, MA, USA

1998.09-2004.06, Ph.D. student

Institute of Biophysics, Chinese Academy of Sciences, Beijing

TEACHING COURSES

Structural Biology Research Techniques

GROUP MEMBERS

Faculty - Lu-lu Kong Ph.D., Dan-Dan Chen Ph.D., Rui Han Ph.D.

Students - Chao Shi, Feng-Wei Nan, Xi Luo, Yao Lu, Qing-Bo Xu, Ming-Xuan Li

PUBLICATIONS

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.