Team-Leader

Prof. Zhichao Zhang

Professor of Organic Chemistry

School of Chemistry, University of Dalian University of Technology

Address: No.2 Linggong Road, Ganjingzi District, Dalian City, Liaoning Province, P.R.C., 116024

E-mail: zczhang@dlut.edu.cn

Tel: +86 13942696903 

Main experience

1989 - 1996, Norman Bethune University of Medical Science received a bachelor's degree and a master's degree in seven-year master's program.

1996-1999 Dalian Railway Hospital, physician

1999-2002, Ph.D., Department of Bioengineering, Dalian University of Technology, and received a doctorate in engineering in 2002.

2002-present Associate Professor, Department of Fine Chemical Engineering, Dalian University of Technology, Head of Chemical Biology Research Group.

2006-2007 postdoctoral fellow, Department of Chemistry and Chemical Biology, Harvard University, USA.

2010-2014 Associate Professor, School of Chemistry, Department of Chemical Engineering and Environmental Life, Dalian University of Technology

2014 Professor, School of Chemistry, Department of Chemical Engineering and Environmental Life, Dalian University of Technology

Main research directions:

     1. Development of small molecule targeted anticancer drugs.

     2. Visualization of tumor targets such as Bcl-2.

     3. Tumor signal transduction pathway and drug target network

Fund:

1. The design and synthesis of subtype-specific Hsp70 inhibitors and the study of anti-tumor molecular markers by National Natural Science Foundation (82073703). January, 2021-December, 2024. Project leader.

2. The project of cooperation between medical workers and doctors in Liaoning Province: the molecular mechanism of p53-Bcl-2 axis in cisplatin resistance of ovarian epithelial cancer and the discovery of original anti-cancer lead drugs to reverse drug resistance. Project leader. （DUT20YG133）

3. Dalian Science and Technology Innovation Fund "the belt and road initiative" International Science and Technology Cooperation Project (2019J12SN51): Creation of Bcl-2 inhibitor targeted anticancer drugs. Project leader.

4. Study on the mechanism of Bcl-2 family proteins in Bcr/Abl independent drug resistance of chronic myeloid leukemia by National Natural Science Foundation (81570129). 2016，1-2019，12. Project leader.

5. Key project of National Natural Science Foundation (81430083): Multi-target anti-tumor compounds based on protein interaction network of Bcl-2 family. 2015-2019. Head of the cooperative unit.

6. National Natural Science Foundation of China (21372036) Research on Fragment-based Broad-spectrum Bcl-2 Inhibitors-Molecular Design and Optimized Quantitative Activity Evaluation. 2014,1-2017,12. Project leader.

7. Molecular characteristics and structure-activity relationship of new organic small molecule BH3 mimics supported by National Natural Science Foundation (30772622). 2008 -2010. Project leader.

8. National Natural Science Foundation (30400106) Hg2+ fluorescent molecular probe and visualization of Hg2+ in single living cell. 2005 -2008. Project leader.

Transfer of patent

1. Acenaphthene heterocyclic compounds and their application in inducing apoptosis and anti-tumor. ZL200410050449.5

2. Acenaphthene heterocyclic compounds, cyclodextrin inclusion compounds and cyclodextrin conjugates thereof, and their applications in preparing Bcl-2 family protein inhibitors. CN200910209961.2.

3. Acenaphthene heterocyclic compounds, cyclodextrin inclusion compounds and cyclodextrin conjugates thereof, and their applications in preparing Bcl-2 family protein inhibitors. PCT/CN2009/074602.

4. Bcl-2 family protein inhibitors, cyclodextrin inclusion complexes, complexes and their applications in the preparation of Bcl-2 family protein inhibitors PCT/CN2010/075521.

Published Papers

1. Ziqian Wang, Xiaodong Zhang, Hong Zhang, Yao Tang, Hao Pan, Hang Wang, Tong Ji, Yafei Guo,Qishuang Gao, Ting Song,* and Zhichao Zhang*. Discovery of a Fluorogenic Probe for In Situ Pyruvate Kinase M2 Isoform (PKM2) Labeling through Chemoselective SNAr with a Binding Site Lysine Residue. Anal. Chem. 2021, 93, 9669−9676

2. Hong Zhang, Zongwei Guo, Yafei Guo, Ziqian Wang, Yao Tang, Ting Song *, Zhichao Zhang*. Bim transfer between Bcl-2-like protein and Hsp70 underlines Bcl-2/Hsp70 crosstalk to regulate apoptosis. Biochemical Pharmacology 190 (2021) 114660

3. Song, T ,  Guo,Y, Xue Z, Zongwei Guo, Wang,Z, Lin D, Zhang H, Pan H, Zhang,X, Yin F, Wang H, Bonnette U, and Zhang ZC*. Small-molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in CML cells overcomes BCR-ABL-independent TKI resistance. Leukemia. https://doi.org/10.1038/s41375-021-01283-5

4. Wang, Z., Song, T, Guo, Z.,Laura, B.,Guo, Y., Zhang, H.,Wang, H.,Zhang, X., Pan, H., Ji, T., Yin, F.,  Zhou, S., Dai, J.and Zhang, Z*. (2021) A novel Hsp70 inhibitor specifically targeting the cancer-related Hsp70-Bim protein-protein interaction[J]. European Journal of Medicinal Chemistry.220,113452.

5. Guo, ZW, Song, T, Zhang ZC*. Systems analysis of the ‘weights’ of Bcl-2 and Mcl-1 in mitochondrial apoptosis pathway establishes a predictor for best drug combination ratio. Quantitative Biology. Accepted.

6. Wang ZQ, Song, T, Zhang ZC*.Targeting the allosteric pathway that interconnect the core-functional scaffold and the distal phosphorylation sites for specific dephosphorylation of Bcl-2. Journal of medicinal chemistry. 2020, 63, 13733-13744.

7. Guo, ZW, Song, T, Wang, ZQ., Lin, DH, Cao, KK., Liu, P, Feng YG, Zhang XD, Wang P, Yin FK, Dai J, Zhou S, Zhang ZC*. The chaperone Hsp70 is a BH3 receptor activated by the pro-apoptotic Bim to stabilize anti-apoptotic clients. The Journal of Biological Chemistry, 2020, 295, 12900-12909.

8. Zhang XD, Wang ZQ, Guo ZW, Song T , He NZ, Zhu JJ, Cao KK, and Zhang ZC*. A “three-in-one” multi-functional probe for Bcl-2/Mcl-1 profiling and visualizing in situ. ChemBioChem, 2021, 22, 326-329. (81903462 and 81430083)

9. Zhu JJ, Wang ZQ, Guo ZW, Zhang XD, Song T, Guo YF, Ji T, Zhang ZC*. Structure-based design, synthesis, and evaluation of Bcl-2/Mcl-1 dual inhibitors. Arch Pharm, 2020. 353(5), e2000005.

10. Guo ZW, Song T, Xue ZG, Liu P, Zhang MH, Zhang XD, Zhang ZC*. Using CETSA assay and a mathematical model to reveal dual Bcl-2/Mcl-1 inhibition and on-target mechanism for ABT-199 and S1. European Journal of Pharmaceutical Sciences, 2020, 142: 105105.

11. Wang Peiran, Zhang ZC*. Identification of the apoptosis and autophagy bifunctional proteins, Molecular Informatics, 2019, 1900008.

12. He NZ, Liu P, Wang ZQ, Guo ZW, Yan XX, Chen HB and Zhang ZC*. Discovery of selective Mcl-1 inhibitors via structure-based design and structure-activity relationship analysis. Biochemical and Biophysical Research Communications, 2019, 512, 921-926.

13. Zhang XD, Wang ZQ, Guo ZW, He NZ, Liu P, Xia DS, Yan XF and Zhang ZC*. A novel turn-on fluorescent probe for selective sensing and imaging of glutathione in live cells and organisms. Analyst, 2019, 144, 3260-3266.

14. Song T, Wang PR, Yu XY, Wang AH, Chai GB, Fan YD and Zhang ZC*. Systems analysis of phosphorylation-regulated Bcl-2 interactions establishes a model to reconcile the controversy over the significance of Bcl-2 phosphorylation. British journal of pharmacology, 2019, 176, 491-504.

15. Song Ting, Cao Keke, Fan Yu dan, Zhichao Zhang,*, Zong W. Guo, Min H. Zhang and Peng Liu. Expression and Solution NMR Study of Multi-site Phosphomimetic Mutant BCL-2 Protein. Protein & Peptide Letters, 2019, 26, 449-457. (21402022,21372036, 81570129,21502015, and 81430083).

16. Ziqian Wang, Zhichao Zhang*, Ting Song, Zongwei Guo, Affinity-based probe reveal Bim negatively regulates the chaperone functions of Hsp70, a non-Bcl-2 BH3 receptor. Cancer Research 2019, 79(13), S2754.

17. Wang ZQ, Guo ZW, Song T, Zhang, XD, He NZ, Liu P, Wang PR and Zhang ZC*. Proteome-wide identification of on- and off-targets of Bcl-2 inhibitors in native biological systems by using affinity-based probes (AfBPs). Chembiochem, 2018, 21, 2312-2320.

18. Song T, Zhang MH, Liu P, Xue ZY, Fan YD, and Zhang ZC*, Identification of JNK1 as a predicting biomarker for ABT-199 and paclitaxel combination treatment. Biochemical pharmacology, 2018, 155, 102-109.

19. 刘璐 张志超. 线性短模体：介导蛋白质相互作用的新模块.生物化学与生物物理进展2017, 44, 129-138

20. Wang ZQ, Xu WJ, Song T, Guo ZW, Liu L, Fan YD, Wang AH and Zhang ZC*. Fragment-based design, synthesis, and biological evaluation of 1-substituted-indole-2-carboxylic acids as selective Mcl-1 inhibitors. Archiv der Pharmazie, 2017, 350, 1-12.

21. Song T, Wang ZQ, Ji FL, Feng YG, Fan YD, Chai GB, Li XQ, Li ZQ and Zhang ZC*. Deactivation of Mcl-1 by dual-function small-molecule inhibitors targeting Bcl-2 homology 3 domain and facilitating Mcl-1 ubiquitination. Angewandte chemie international edition, 2016, 55, 14248-1425.

22. Song T, Wang ZQ and Zhang ZC*. Substituted indole Mcl-1 inhibitors: a patent evaluation. Expert opinion on therapeutic patents, 2016, 26, 1227-1238.

23. Wang ZQ, Song T, Feng YG, Guo ZW, Fan YD, Xu WJ, Liu L, Wang AH and Zhang ZC*.  Bcl-2/MDM2 dual inhibitors based on universal pyramid-like α-helical mimetics. Journal of medicinal chemistry, 2016, 59, 3152-3162.

24. Wang AH, Song T, Wang ZQ, Liu YB, Fan YD, Zhang YH and Zhang ZC*. Mechanism of Mcl-1 conformational regulation upon small molecule binding revealed by molecular dynamic simulation. Chemical biology & drug design, 2016, 87, 551-561.

25. Zhang ZC*, Su PC, Li XQ, Song T, Chai GB, Yu XY and Zhang KR. Novel Mcl-1/Bcl-2 Dual inhibitors created by the structure-based hybridization of drug-divided building blocks and a fragment deconstructed from a known two-face BH3 mimetic. Archiv. Der. Pharmazie, 2015, 348, 89-99.

26. Song T, Yu XY, Liu YB, Li XQ, Chai GB and Zhang ZC*. Discovery of a small-molecule pBcl-2 inhibitor that overcomes pBcl-2-mediated resistance to apoptosis. Chembiochem, 2015, 16, 757-765.

27. Song T, Chai GB, Liu YB, Xie MZ, Chen QB, Yu XY, Sheng HK and Zhang ZC*. Mechanism of synergy of BH3 mimetics and paclitaxel in chronic myeloid leukemia cells: Mcl-1 inhibition. European Journal of Pharmaceutical Sciences, 2015, 70, 64-71. 

28. Song T, Chai GB, Liu YB, Yu XY, Wang ZQ and Zhang ZC*. Bcl-2 phosphorylation confers resistance of chronic lymphocytic leukemia cells to the BH3 mimetic ABT-737, ABT-263 and ABT-199 by impeding direct binding. British journal of pharmacology, 2016, 171, 471-483. 

29. Li XQ, Liang XM, Song T, Su PC and Zhang ZC*. Design, synthesis and structure–activity relationship studies of morpholino-1H-phenalene derivatives that antagonize Mcl-1/Bcl-2. Bioorganic & medicinal chemistry, 2014, 22, 5738-5746.

30. Li XQ, Wang ZQ, Feng YG, Song T, Su PC, Chen QB , Chai GB, Yang Y and Zhang ZC*. Two-face, two-turn α-helix mimetics based on a cross-acridine scaffold: analogues of the Bim BH3 domain. Chembiochem, 2014, 15, 1280-1285.

31. Huang X, Wang C, Li S, Liu YB and Zhang ZC*. Highly sensitive visualization of inorganic mercury in mouse neurons using a fluorescent probe. Journal of fluorescence, 2014, 24, 1313-1317.

32. Song T, Yang Y, Wu GY, Xie SH, Su PC, Feng YG* and Zhang ZC*. Corrigendum to “3-Thiomorpholin-8-oxo-8H-acenaphtho [1, 2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1”. Bioorganic & Medicinal Chemistry, 2014, 22, 663-664.

33. Liu YB and Zhang ZC*. Resistance to BH3 mimetic S1 in non-small cell lung cancer cells that phosphorylate Bim through ERK1/2 and lead to its proteasomal degradation. Journal. Thoracic Oncology, 2013, 8, S1061.

34. Liu YB and Zhang ZC*. Resistance to BH3 mimetic S1 in SCLC cells that up-regulate and phosphorylate Bcl-2 through ERK1/2. Journal thoracic oncology, 2013, 8, S767.

35. Song T, Chen Q, Li XQ, Chai GB and Zhang ZC*. Correction to 3-thiomorpholin-8-oxo- 8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (S1) based molecules as potent, dual inhibitors of B-Cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1): structure-based design and structure-activity relationship studies. Journal of medicinal chemistry, 2013, 56, 9366-9367.

36. Liu YB, Zhang ZC*, Song T, Liang FR, Xie MZ and Sheng HK. Resistance to BH3 mimetic S1 in SCLC cells that up-regulate and phosphorylate Bcl-2 through ERK1/2. British journal of pharmacology, 2013, 169, 1612-1623.

37. Liu YB, Li ZQ, Song T, Xue ZG and Zhang ZC*. Mechanisms of anti-leukemic activity of the Bcl-2 homology domain-3 mimetic S1. Biomedicine & Pharmacotherapy, 2013, 67, 583-591.

38. Zhang ZC, Liang XM, Li XQ, Song T, Chen QB and Sheng HK. Design and application of a rigid quinazolone scaffold based on two-face Bim a-helix mimicking. European journal of medicinal chemistry, 2013, 69, 711-718.

39. Zhang ZC *, Zhao Y, Song T, Liu YB, Li XQ, Su PC and Xie SH. Study of binding thermodynamics in the optimization of BH3 mimetics. Chemical biology & drug design, 2013, 82, 4, 394-400.

40. Song T, Xue ZG, Zhang ZC*, Shen XY and Li XQ. Pan-BH3 mimetic S1 exhibits broad-spectrum antitumour effects by cooperation between Bax and Bak. Basic & clinical pharmacology & toxicology, 2013, 113, 145-151.

41. Zhang ZC*, Liu YB, Song T, Xue ZG, Shen XY, Liang FR, Zhao Y, Li ZQ and Sheng HK.  An antiapoptotic Bcl-2 family protein index predicts the response of leukaemic cells to the pan-Bcl-2 inhibitor S1. British journal of cancer, 2013, 108, 1870-1878.

42. Zhang ZC*, Liu CW, Li XQ, Song T, Wu ZY, Liang XM, Zhao Y, Shen XY and Chen HB*. Fragment-based design, synthesis, and biological evaluation of N-substituted-5-(4-isopropylthiophenol)-2-hydroxynicotinamide derivatives as novel Mcl-1 inhibitors. European journal of medicinal chemistry, 2013, 60, 410-420.

43. Song T, Li XQ, Chang XL, Liang XM, Zhao Y, Wu GY, Xie SH, Su PC, Wu ZY, Feng YG, Zhang ZC*. 3-thiomorpholin-8-oxo-8H-acenaphtho [1, 2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1. Bioorganic & medicinal chemistry, 2013, 21, 11-20.

44. Zhang ZC*, Song T, Li XQ, Wu ZY, Feng YG, Xie FB, Liu CW, Qin JQ and Chen HB. Novel soluble myeloid cell leukemia sequence 1 (Mcl-1) inhibitor (E, E)-2 (benzylaminocarbonyl)-3-styrylacrylonitrile (4g) developed using a fragment-based approach. European journal of medicinal chemistry, 2013, 59, 141-149.

45. Zhang ZC*, Li XQ, Song T, Zhao Y and Feng YG. An anthraquinone scaffold for putative, two-face Bim BH3 α-helix mimicries. Journal of medicinal chemistry, 2012, 55, 10735-10741. 

46. Song T, Chang XL, Zhang ZC*, Liu YB and Shen XY. S1, a novel pan-BH3 mimetic, induces apoptosis in Mcl-1-overexpressing cells through Bak. Journal of pharmacological sciences, 2012, 119, 330-340.  

47. Zhong JT, Xu Y, Yi HW, Su J, Yu HM, Xiang XY, Li XN, Zhang ZC* and Sun LK*. The BH3 mimetic S1 induces autophagy through ER stress and disruption of Bcl-2/Beclin 1 interaction in human glioma U251 cells. Cancer letters, 2012, 323, 180-187.

48. 李亚平, 钟加滕, 张志超, 衣豪伟, 李晓宁, 崔丽丽. Bcl-2抑制剂S1通过内质网途径诱导黑色素瘤B16细胞凋亡的机制. 中国老年学杂志, 2012, 04, 767-769.

49. 琴瀚姣, 刘宁, 张晶, 张钰, 杨晓春, 张志超, 孙连坤. Bcl-2抑制剂S1诱导人卵巢癌细胞凋亡及其机制的研究. 吉林医学, 2012, 13, 2693-2695.

50. Zhang ZC*, Yang HN, Wu GY, Li ZQ, Song T and Li XQ. Probing the difference between BH3 groove of Mcl-1 and Bcl-2 protein: implications for dual inhibitors design. European journal of medicinal chemistry, 2011, 46, 3909-3916.

51. Zhang ZC*, Wu GY, Xie FB, Song T and Chang XL.  3-Thiomorpholin-8-oxo-8H-acenaphtho [1, 2-b] pyrrole-9-carbonitrile (S1) based molecules as potent, dual inhibitors of B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1): structure-based design and structure-activity relationship studies. Journal of medicinal chemistry, 2011, 54, 1101-1105.

52. Zhang ZC*, Song T, Zhang TT, Wu GY, An LJ and Du GH. A novel BH3 mimetic S1 potently induces Bax/Bak-dependent apoptosis by targeting both Bcl-2 and Mcl-1. International journal of cancer, 2011, 128, 1724-1735.

53. Zhang ZC*, Wu GY, Gao J and Song T. Inclusion complex of a Bcl-2 inhibitor with cyclodextrin: characterization, cellular accumulation, and in vivo antitumor activity. Molecular pharmaceutics, 2010, 7, 1348-1354.

54. Zhang ZC*, Gao J, Wang YY, Song T, Zhang J, Wu GY, Zhang TT and Du GH. Tanshinone IIA triggers p53 responses and apoptosis by RNA polymerase II upon DNA minor groove binding. Biochemical pharmacology, 2009, 78, 1316-1322.

55. Zhang ZC, Wang YY, Song T, Gao J, Wu GY, Zhang J and Qian XH. DNA double helix unwinding triggers transcription-block-dependent apoptosis: A semi-quantitative probe of the response of ATM, RNAPII, and p53 to two DNA intercalators. Chemical research in toxicology, 2009, 22, 483-491.

56. Li YC, Zhang ZC*, Song T and Wu GY. Characterization of DNA intercalator bound to calf thymus DNA: ionic strength and pH value effect. Chemical research in chinese universities, 2009, 25, 497-499.

57. Zhang ZC*, Zhang J, Jin LJ, Song T, Wu GY and Gao J. Tanshinone IIA Interacts with DNA by Minor Groove-binding. Biological and Pharmaceutical Bulletin, 2008, 31, 2342-2345.

58. Zhang ZC*, Wang YY, Zhang J, Song T and Qian XH. Potency and property of DNA conformational damage determine ATM activation: two new DNA topological probes. Cell Biochemistry and Function, 2008, 26, 808-812.

59. Zhang ZC*, Zhang J, Yuan CL, Wu GY and Qian XH. Intercalation, cytotoxicity and molecular modeling of acenaphtho [1, 2-b] pyrrole chromophores as new family of antitumor agents. Chemical research in chinese universities, 2008, 24, 449-453.

60. Jin LJ, Zhang ZC*, Wang YY, Wei MJ and Xu Q. A novel small molecule inhibitor targeted at Bcl-2. Science in China Series C: Life Sciences, 2007, 50, 624-629.

61.金礼吉, 张志超*, 王媛媛, 魏美娇, 徐芹. 一个新的有机小分子Bcl-2蛋白抑制剂. 中国科学, 2007, 37, 416-421.  

62.杨源源, 张志超*, 盛辉, 刘凤玉, 钱旭红, 徐芹, 张晶.  一种苊并杂环有机小分子嵌入DNA的几何学模式研究. 高等学校化学学报, 2007, 28, 453-457.

63. Zhang ZC*, Jin LJ, Qian XH, Wei MJ, Wang YY, Wang J, Yang YY, Xu Q, Xu YT and Liu FY. A novel non-intercalator apoptosis-inducing organic compound via Bcl-2 protein and structure-based development of Bcl-2 inhibitor. Chembiochem, 2007, 8, 113-121.

64. Zhang ZC, Yang YY, Zhang DN, Wang YY, Qian XH and Liu FY. Acenaphtho [1, 2-b]pyrrole derivatives as new family of intercalators: Various DNA binding geometry and interesting antitumor capacity. Bioorganic & medicinal chemistry, 2006, 14, 6962-6970.

65. Zhang ZC, Yang YY, Liu FY, Qian XH and Xu Q. Study on the interaction between   4-(2-diethylamino-ethylamino)-8-oxo-8H-acenaphtho [1, 2-b] pyrrole-9-carbonitrile and DNA by molecular spectra. International journal of biological macromolecules, 2006, 38, 59-64.

66. Zhang ZC, Wu D, Guo XF, Qian XH, Lu Z, Xu Q, Yang YY, Duan LP, He YK and Feng Z. Visible study of mercuric ion and its conjugate in living cell of mammalian and plant. Chemical research in toxicology, 2005, 18, 1814-1820.

Patent

1. 4- substituted naphthalimide compounds and their applications 20171058107.3 Authorization date: August and April, 2021.

2. A class of 1,5- diphenyl pyrazole -3- carboxylic acid compounds and their applications. 5.5. Authorization date: October 24, 2017 .20047.200100000007

3. Benzimidazole compounds and their applications. ZL 2014 1 0326318.9. Authorization date: December 7, 2016.

4. A class of acridine compounds and their applications.201410150928.8. First inventor. Authorization date: April 13, 2016.

5. acenaphthene heterocyclic compounds and their application in inducing apoptosis and anti-tumor. ZL200410050449.5. Second inventor.

6. acenaphthene heterocyclic compounds, cyclodextrin inclusion compounds and cyclodextrin conjugates, and their applications in preparing Bcl-2 family protein inhibitors. CN200910209961.2. First inventor. Authorized. Authorized date: September 5, 2012.

7. Acenaphthene heterocyclic compounds, their cyclodextrin inclusion compounds and cyclodextrin complexes and their applications in preparing

Bcl-2 family protein inhibitors. PCT/CN2009/074602. At present, it has entered 32 countries and regions such as the United States, Europe, Japan, Russia, Ukraine, New Zealand, Mexico and South Africa. The first inventor.

8. Bcl-2 family protein inhibitor, cyclodextrin inclusion compound, conjugate and its application in preparing Bcl-2 family protein inhibitor. PCT/CN2010/075521. First inventor.

9. A class of amino-substituted acenaphthene heterocyclic compounds and their applications. China patent: 201110191880.1. First inventor.

Authorized. Authorized date: September and October, 2013.

10. A class of acenaphthene heterocyclic compounds and their applications. China patent: 201110191883.5, first inventor, authorized. Authorization date: June 15, 2013.

11. A class of acenaphthene heterocyclic compounds and their applications. PCT/CN2011/077682, the first inventor.

12. Application of (e, e)-2-(benzyl amino carbonyl) -3- styrylacrylonitrile and its derivatives, the first inventor .10748.2 .100011000107

13. A method for screening tumor cells that can be induced by acenaphthene heterocyclic compounds and its application. PCT/CN2011/000119.

14. A class of anthraquinone compounds and their applications. 201210218670.1, authorized. Authorized date: May and June, 2014.

15. Acenaphtho hetero cyclic compounds and application there. Application number: 13810.901, authorization date: January 18, 2013.

2020 patent application:

1. ApplicationNo.: 20201004449.3 Invention Name: A Class of Finenone Compounds and Their Application Date: January 15, 2020.

2. ApplicationNo.: 2020102979197 Invention Name: 3- cyanophenanthrenone compound and its application date: April 16th, 2020.

3. 2- cyanophenanthrenone compounds and their application in the treatment of leukemia. Application in 2021, 202110164854.3