xm:缪泽鸿
xb:男
zc:研究员
xl:博士
dh:
cz:
dzyj:zhmiao@simm.ac.cn
grzy:
zjlb:研究员；****；新药；
zw:研究组长、博士生导师
txdz:上海市浦东新区海科路501号
grjj:缪泽鸿，博士，中国科学院上海药物研究所研究员、博士生导师、研究组长。从事肿瘤药理研究，着重围绕肿瘤DNA修复与协同致死、表观遗传及泛素调控系统等展开创新型抗肿瘤药物研发及相关机制研究。已在SCI学术期刊发表论文120余篇，包括Cancer Res (6篇)、Cancer Lett (2篇)、Mol Cancer Ther (5篇)、Int J Cancer (4篇)、Cell Death Dis (4篇)、J Med Chem (7篇)、Nat Prod Rep、Trends Pharmacol Sci等药理学和肿瘤学领域的重要期刊；参加编写国际专著2本、国内专著5本；主持完成具有自主知识产权的3个抗肿瘤1类新药（盐酸希明替康、盐酸美呋哌瑞和希明哌瑞）的临床前研究，正在开展临床试验；2个抗肿瘤1类新药（HJP-178和SOMCL-19-133）进入临床前研究；获授权发明专利35件、申请受理国内外发明专利 25 项。先后主持或参与各级各类课题50余项；入选上海市浦江人才计划（2008）、国家****科学基金（2010）、中国科学院科技创新交叉与合作团队（2012）、上海市优秀学术带头人计划（2013）、中国科学院特聘研究员（2015）等人才计划；曾获各级各类奖项20余项。

yjfx:肿瘤药理学；主要围绕肿瘤DNA修复与协同致死、表观遗传及泛素调控系统等展开抗肿瘤新药研发及抗肿瘤作用与机制、耐药机制、靶点发现与生物标志物发现研究，并依据学科发展情况动态调整。基础性研究围绕抗肿瘤新药研发过程展开，力图充分揭示自主研发新药、新化合物在作用、机制、耐药及其预测与防控、疗效预测、患者选择、联合用药等各个方面的性质与特点，服务于推动新药的研发进程和未来临床患者用药获益的最大化。

1.DNA修复与协同致死：DNA修复功能异常引起的遗传不稳定性，是导致多种肿瘤发生和推动其发展的重要机制。协同致死(synthetic lethality)是指两个不致死的非等位基因同时突变导致细胞死亡的现象。当一个突变基因与肿瘤发生发展紧密相关时，靶向其对应的协同致死基因(或其产物)将产生高选择性抗肿瘤效应。聚腺苷二磷酸核糖聚合酶1[poly (ADP-ribose) polymerase 1, PARP1]是重要的DNA修复因子；在BRCA1/2突变肿瘤细胞，抑制PARP1产生协同致死效应。PARP1抑制剂成为首个成功开发的协同致死类新型抗肿瘤药物代表。我们自主研发的两种PARP1抑制剂盐酸美呋哌瑞和希明哌瑞正在进行临床试验。协同致死基因对正在不断被发现，并且向表观遗传等方向加速拓展，成为抗肿瘤靶点的新源泉。我们正在积极开展基于新的协同致死基因对的新药研发与研究工作。

2.表观遗传：是一种不改变DNA核苷酸序列，实现可遗传的基因表达调控方式，包含DNA甲基化、组蛋白乙酰化和甲基化、基因组印记(genomic imprinting)、RNA编辑(RNA editing)等丰富的调控机制。表观遗传调控异常与肿瘤发生发展密切相关，已有多种相关药物上市用于肿瘤治疗。溴结构域和额外末端结构域 (bromodomain and extra-terminal domain, BET)蛋白与组蛋白乙酰化密切相关，人类至少46个蛋白包含总计61个溴结构域，广泛参与调控涉及DNA修复、免疫、代谢、信号转导等的基因表达，成为受到密切关注的抗肿瘤靶点群。我们研发的一个全新结构的BET抑制剂 HJP-178进入临床前研究阶段，并发现BET抑制剂与多种其他新靶点抗肿瘤药物存在显著的协同增效作用，相关工作在持续推进。

3.泛素调控系统：泛素与泛素样（ubiquitin and ubiquitin-like；Ub/Ubl）系统属于蛋白翻译后修饰系统，修饰目标蛋白，调控其功能及活性，并且作为蛋白降解标志，引导其通过蛋白酶体降解，成为蛋白循环更新的关键。Ub/Ubl由激活酶E1 (包括泛素激活酶 UAE、NEDD8激活酶NAE 及SUMO激活酶SAE)、结合酶E2、连接酶E3、去泛素酶DUBs以及蛋白酶体等组成。Ub/Ubl系统组成复杂，蛋白（包括酶类）成员众多（＞600个）。已发现部分成员酶类在肿瘤发生、演进、耐药与转移过程中发挥关键作用；部分酶类在肿瘤中的表达、活性等与正常组织具有显著差异。这些特点共同构成针对Ub/Ubl系统发展选择性抗肿瘤药物的基础。目前，我们研发的一个NAE抑制剂进入临床前研究阶段，并正在开展针对其他泛素调控靶点的新药发现研究工作；相关机制研究工作也在积极推进中。

dblz:总计发表SCI论文120余篇，按5个主要主题领域分类列示。

1. On PARP inhibitors

1)Hua-Dong Chen, Ne Guo, Shan-Shan Song, Chuan-Huizi Chen, Ne Guo, Ze-Hong Miao*, Jin-Xue He*. Novel mutations in BRCA2 intron 11 and overexpression of COX-2 and BIRC3 mediate cellular resistance to PARP inhibitors. Am J Cancer Res (accepted. 2020.7.26).

2)Yu-Nan Tian, Hua-Dong Chen, Chang-Qing Tian, Ying-Qing Wang*, Ze-Hong Miao*. Polymerase independent repression of FoxO1 transcription by sequence-specific PARP1 binding to FoxO1 promoter. Cell Death Dis. 2020；11(1):71.

3)Hua-Dong Chen, Chuan-Huizi Chen, Yu-Ting Wang, Ne Guo, Yu-Nan Tian, Xia-Juan Huan, Shan-Shan Song, Jin-Xue He, Ze-Hong Miao*. Increased PARP1-DNA binding due to autoPARylation inhibition of PARP1 on DNA rather than PARP1-DNA trapping is correlated with PARP1 inhibitor’s cytotoxicity. Int J Cancer. 2019;145(3):714-727

4)Yu-Ting Wang, Bo Yuan, Hua-Dong Chen, Yu-Nan Tian, Ao Zhang, Jin-Xue He*, Ze-Hong Miao*. Acquired Resistance of PTEN-Deficient Glioblastoma Cells to PARP Inhibitors and Cytarabine Mediated Separately by 53BP1 Loss and SAMHD1 Overexpression. Cancer Sci. 2018;109(3):821-831.

5)Zhong-Min Yang, Xue-Mei Liao, Yi Chen, Yan-Yan Shen, Xin-Ying Yang, Yi Su, Yi-Ming Sun, Ying-Lei Gao, Jian Ding, Ao Zhang, Jin-Xue He*, Ze-Hong Miao*. Combination of 53BP1 With BRCA1 to Predict the Sensitivity of Poly(ADP-ribose) Polymerase (PARP) Inhibitors. Acta Pharmacol Sin. 2017; 38: 1038-1047.

6)Bo Yuan, Na Ye, Shan-Shan Song, Yu-Ting Wang, Hua-Dong Chen, Chuan-Huizi Chen, Xia-Juan Huan, Ying-Qing Wang, Yi Su, Yan-Yan Shen, Yi-Ming Sun, Xin-Yin Yang, Yi Chen, Shi-Yan Guo, Yong Gan, Zhi-Wei Gao, Xiao-Yan Chen, Jian Ding, Jin-Xue He*, Ao Zhang*, and Ze-Hong Miao*. Poly(ADP-ribose)polymerase (PARP) Inhibition and Anticancer Activity of Simmiparib, a New Inhibitor Undergoing Clinical Trials. Cancer Lett. 2017; 386:47-56.

7)Jin-Xue He, Meng Wang, Xia-Juan Huan, Chuan-Huizi Chen, Shan-Shan Song, Ying-Qing Wang, Xue-Mei Liao, Cun Tan, Qian He, Lin-Jiang Tong, Yu-Ting Wang, Xiao-Hua Li, Yi Su, Yan-Yan Shen, Yi-Ming Sun, Xin-Yin Yang, Yi Chen, Zhi-Wei Gao, Xiao-Yan Chen, Bing Xiong, Xiu-Lian Lu, Jian Ding, Chun-Hao Yang*, Ze-Hong Miao*. Novel PARP1/2 inhibitor mefuparib hydrochloride elicits potent in vitro and in vivo anticancer activity, characteristic of high tissue distribution. Oncotarget. 2017; 8(3):4156-4168.

8)Ying-Qing Wang, Pingyuan Wang, Yu-Ting Wang, Guangfu Yang, Ao Zhang*, Ze-Hong Miao*. An update on poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors: opportunities and challenges in cancer therapy. J Med Chem. 2016;59 (21):9575-9598.

9)Jin-xue He, Chun-hao Yang, Ze-hong Miao*. PARP inhibitors as promising cancer therapeutics. Acta Pharmacol Sin 2010;31(9):1172-1180.

10)Xuxing Chen, Xiajuan Huan, Qiufeng Liu,Yuqin Wang, He Qian, Cun Tan, Yi Chen, Jian Ding, Yechun Xu*, Zehong Miao*, Chunhao Yang*. Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious poly(adp-ribose)polymerase (PARP) inhibitors. Eur J Med Chem. 2018;145:389-403.

11)Wen-Hua Chen, Shan-Shan Song, Ming-hui Qi, Xia-Juan Huan, Ying-Qing Wang, Jian Ding, Guo-Bin Ren*, Ze-Hong Miao*, Jian Li*. Discovery of Potent 2,4-Difluoro-linker Poly(ADP-ribose) Polymerase (PARP) 1 Inhibitors with Enhanced Water Solubility and in Vivo Efficacy for Cancer Therapy. Acta Pharmacol Sin. 2017;38:1521-1532.

12)Wenhua Chen, Ne Guo, Minghui Qi, Haiying Dai, Minghuang Honc, Longfei Guan, Xiajuan Huan, Shanshan Song, Jinxue He, Yingqing Wang, Yong Xi, Xinying Yang, Yanyan Shen, Yi Su, Yiming Sun, Yinglei Gao, Yi Chen, Jian Ding, Yun Tang, Guobin Ren*, Zehong Miao*, Jian Li*. Discovery, Mechanism and Metabolism Studies of 2,3-Difluorophenyl-Linker-Containing PARP1 Inhibitors with Enhanced In Vivo Efficacy for Cancer Therapy. Eur J Med Chem. 2017;138:514-531.

13)Jianyang Chen, Haixia Peng, Jinxue He, Xiajuan Huan, Zehong Miao*, Chunhao Yang*. Synthesis of isoquinolinone-based tricycles as novel poly(ADP-ribosyl) polymerase-1 (PARP-1) inhibitors. Bioorg Med Chem Lett. 2014; 24:2669-2673

14)Na Ye, Chuan-Huizi Chen, Tian-Tian Chen, Zilan Song, Jin-Xue He, Xia-Juan Huan, Shan-Shan Song, Qiufeng Liu, Yi Chen, Jian Ding, Yechun Xu*, Ze-Hong Miao*, Ao Zhang*. Design, synthesis and biological evaluation of a series of benzo[de][1,7]naphthyridin-7(8h)-ones bearing a longer chain as novel PARP1 inhibitors. J Med Chem. 2013; 56 (7):2885–2903.

15)Jian Ding*, Ze-Hong Miao, Ling-Hua Meng, Mei-Yu Geng. Emerging cancer therapeutic opportunities target DNA repair systems. Trends Pharmacol Sci (TiPS) 2006; 27(6):338-344.

2. On BET inhibitors

16)Mohammadali Soleimani Damaneh, Jian-Ping Hu, Xia-Juan Huan, Shan-Shan Song, Chang-Qing Tian, Bing Xiong *, Ze-Hong Miao *, Ying-Qing Wang *. A new BET inhibitor, 171, inhibits tumor growth through cell proliferation inhibition more than apoptosis induction. Invest New Drugs. 2020;38(3):700-713.

17)Chang-Qing Tian, Lin Chen, Hua-Dong Chen, Jian-Ping Hu, Jing-Kang Shen, Bing Xiong*, Ying-Qing Wang *, Ze-Hong Miao*. Inhibition of the BET Family Reduces Its New Target Gene IDO1 Expression and the Production of L-Kynurenine. Cell Death Dis. 2019; 10:557.

18)Jianping Hu, Changqing Tian, Mohammadali Soleimani Damaneh, Yanlian Li, Danyan Cao, Kaikai Lv, Ting Yu, Tao Meng, Danqi Chen, Xin Wang, Lin Chen, Jian Li, Shanshan Song, Xiajuan Huan, Lihuai Qin, Jingkang Shen, Yingqing Wang*, Zehong Miao*, Bing Xiong*. Structure-based Discovery and Development of a Series of Potent and Selective Bromodomain and Extra-Terminal Protein Inhibitors. J Med Chem. 2019, 62(18): 8642-8663.

19)Jianping Hu, Yingqing Wang, Yanlian Li, Danyan Cao, Lin Xu, ShanShan Song, Mohammadali Soleimani Damaneh, Jian Li, Yuelei Chen, Xin Wang, Lin Chen, Jingkang Shen, Zehong Miao*, Bing Xiong*. Structure-based optimization of a series of selective BET inhibitors containing aniline or indoline groups. Eur J Med Chem. 2018;150 (2018) 156-175.

20)Hu J, Wang Y, Li Y, Xu L, Cao D, Song S, Damaneh MS, Wang X, Meng T, Chen YL, Shen J*, Miao Z*, Xiong B*. Discovery of a series of dihydroquinoxalin-2 (1H)-ones as selective BET inhibitors from a dual PLK1-BRD4 inhibitor. Eur J Med Chem. 2017; 137:176-195.

21)Lele Zhao, Yingqing Wang, Danyan Cao, Tiantian Chen, Qi Wang, Yanlian Li, Yechun Xu, Naixia Zhang, Xin Wang, Danqi Chen, Lin Chen, Yue-Lei Chen, Guangxin Xia, Zhe Shi, Zehong Miao*, Jingkang Shen*, Bing Xiong*. Fragment-Based Drug Discovery of 2-Thiazolidinones as BRD4 inhibitors: 2. Structure-based Optimization. J Med Chem. 2015;58(3):1281-1297. (IF 5.48)

22)Lele Zhao, Danyan Cao, Tiantian Chen, Yingqing Wang, Zehong Miao, Yechun Xu, Wuyan Chen, Xin Wang, Yanlian Li, Zhiyan Du, Bing Xiong, Jian Li, Chunyan Xu, Naixia Zhang, Jianhua He, Jingkang Shen. Fragment-based drug discovery of 2-thiazolidinones as inhibitors of the histone reader BRD4 bromodomain. J Med Chem. 2013;56(10):3833-51. (IF 5.614)

3. On topoisomerase inhibitors

23)Qian-Ting Tian, Chun-Yong Ding, Shan-Shan Song, Ying-Qing Wang*, Ao Zhang* and Ze-Hong Miao*. New tanshinone I derivatives S222 and S439 similarly inhibit topoisomerase I/II but reveal different p53-dependency in inducing G2/M arrest and apoptosis. Biochem Pharmacol. 2018;154: 255–264.

24)Chunyong Ding, Qianting Tian, Jie Li, Mingkun Jiao, Shanshan Song, Yingqing Wang*, Zehong Miao* and Ao Zhang*. Structural modification of natural product tanshinone I leading to discovery of novel nitrogen-enriched derivatives with enhanced anticancer profile and improved drug-like properties. J Med Chem. 2018;61(3):760-776.

25)Jun-Mei Yi, Xiao-Fei Zhang, Xia-Juan Huan, Shan-Shan Song, Wei Wang, Qian-Ting Tian, Yi-Ming Sun, Yi Chen, Jian Ding, Ying-Qing Wang*, Chun-Hao Yang*, Ze-Hong Miao*. Dual Targeting of Microtubule and Topoisomerase II by α-Carboline Derivative YCH337 for Tumor Proliferation and Growth Inhibition. Oncotarget. 2015; 6(11):8960-73.

26)Lei Xu, Jian-Ming Feng, Jia-Xin Li, Jin-Mei Zhu, Lin-Jiang Tong, Shan-Shan Song, Yi Chen, Fu-Lin Lian, Ya-Ping Li*, Dong-Hai Lin, Jian Ding, Ze-Hong Miao*. Tanshinone-1 induces tumor cell killing, enhanced by inhibition of secondary activation of signaling networks. Cell Death Dis. 2013;4:e905.

27)Ming Li, Ze-Hong Miao*, Zhi Chen, Qin Chen, Min Gui, Li-Ping Lin, Peng Sun, Yang-Hua Yi, Jian Ding*. Echinoside A, a new marine-derived anticancer saponin, targets topoisomerase II by unique interference with its DNA binding and catalytic cycle. Ann Oncol 2010;21(3):597-607.

28)Hong Zhu, Ze-Hong Miao*, Min Huang, Jian-Ming Feng, Zhi-Xiang Zhang, Yu-Jun Cai, Lin-Jiang Tong, Xu-Hong Qian, Yu-Fang Xu, Jian Ding*. Naphthalimides induce G2 arrest through the ATM-activated Chk2-executed pathway in HCT116 cells. Neoplasia. 2009;11(11): 1226–1234.

29)Jian-Ming Feng, Hong Zhu, Xiao-Wei Zhang, Jian Ding, Ze-Hong Miao*. Proteasome-dependent degradation of Chk1 kinase induced by the topoisomerase II inhibitor R16 contributes to its anticancer activity. Cancer Biol Ther. 2008, 7(11): 1726-1731.

30)Min Huang, Ze-Hong Miao, Hong Zhu, Yu-Jun Cai, Wei Lu, Jian Ding. Chk1 and Chk2 are differentially involved in homologous recombination repair and cell-cycle arrest in response to DNA double-strand breaks induced by camptothecins. Mol Cancer Ther. 2008; 7(6):1140-1149.

31)Yong-Wei Zhang, Zhi-Xiang Zhang, Ze-Hong Miao, Jian Ding. The telomeric protein TRF2 is critical for the protection of A549 cells from both telomere erosion and DNA double-strand breaks driven by salvicine. Mol Pharmacol. 2008; 73(3):824-832.

32)Ze-Hong Miao, Audrey Player, Uma Shankavaram, Yong-Hong Wang, Drazen Zimonjic, PhilipLorenzi，Zhi-Yong Liao, Hong Liu，Tsutomu Shimura，Hong-Liang Zhang，Ling-Hua Meng, Yong-Wei Zhang，Ernest S. Kawasaki, Nicholas C. Popescu, Mirit I. Aladjem，David Goldstein, John Weinstein, and Yves Pommier. Non-Classical Functions of Human Topoisomerase I：Genomewide and Pharmacological Analyses. Cancer Res 2007; 67:8752-61.

33)Smitha Antony, Keli K Agama, Ze-Hong Miao, Kazutaka Takagi, Mollie H Wright, Ana I Robles, Lyuba Varticovski, Robert W Robey, Susan E Bates, Muthukaman Nagarajan, Andrew Morrell, Mark Cushman and Yves Pommier. Histone γ-H2AX as a pharmacodynamic biomarker for clinical development of the novel indenoisoquinoline topoisomerase I inhibitors, NSC 725776 and NSC 724998. Cancer Res 2007; 67:10397-10405.

34)Min Huang, Hong Zhu, Heyong Gao, Yi Chen, Yujun Cai, Xiongwen Zhang, Ze-Hong Miao, Hongwu Shen, Liping Lin, Wei Lu and Jian Ding. Chimmitecan, a Novel 9-Substituted Camptothecin, with Excellent Improvement in Anti-cancer Pharmacological Profiles both In Vitro and In Vivo. Clin Cancer Res 2007; 13: 1298-1307.

35)Cheng-Ying Xie, Hong Zhu,1 Li-Ping Lin, Ze-Hong Miao, Mei-Yu Geng, Yu-Jun Cai, Yi Chen, Hua-Jun Zhao, Hai-Bin Luo, Xiong-Wen Zhang, Li-Ming Fan, Yue-Mao Shen, and Jian Ding. MFTZ-1, an actinomycetes subspecies derived antitumor macrolide, functions as a novel topoisomerase II poison. Mol Cancer Ther. 2007;6:3059-3070.

36)Hong Zhu, Min Huang, Fan Yang, Yi Chen, Ze-Hong Miao, Xu-Hong Qian, Yu-Fang Xu, Yu-Xin Qin, Hai-Bin Luo, Xu Shen, Mei-Yu Geng, Yu-Jun Cai, Jian Ding. R16, a Novel Amonafide Analogue, Induces Apoptosis and G2/M arrest via Poisoning Topoisomerase II. Mol Cancer Ther 2007; 6:484-495.

37)Yonghong Wang, Ze-Hong Miao, Yves Pommier, Ernest S. Kawasaki, Audrey Player. Characterization of Mismatch and High-signal Intensity Probes Associated with Affymetrix Genechips. Bioinformatics 2007; 23:2088-2095.

38)V. Ashutosh Rao, Chiara Conti, Josee Guirouilh-Barbat, Asako Nakamura, Ze-Hong Miao, Sally M. Davies, Barbara Sacca, Ian Hickson, Aaron Bensimon, and Yves Pommier. Endogenous ?-H2AX-ATM-Chk2 checkpoint activation in BLM-deficient cells is related to DNA replication arrested forks. Mol Cancer Res 2007; 5:713-724.

39)Ze-Hong Miao, V. Ashutosh Rao, Keli Agama, Smitha Antony, Yves Pommier. 4-Nitroquinoline-1-oxide induces the formation of cellular Topoisomerase I-DNA cleavage complexes. Cancer Res 2006; 66: 6540-6545.

40)Ze-Hong Miao, Keli Agama, Olivier Sordet, Lawrence Povirk, Kurt W. Kohn and Yves Pommier. Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes. DNA Repair 2006; 5:1489-94.

41)Smitha Antony, Keli K Agama, Ze-Hong Miao, Melinda Hollingshead, Mollie Wright, Ana Robles, Lyuba Varticovski, Muthukaman Nagarajan, Mark Cushman and Yves Pommier. Bisindenoisoquinoline NSC 727357, a DNA bisintercalator and topoisomerase inhibitor with antitumor activity. Mol Pharmacol 2006; 70:1109-1120.

42)Haruyuki Takemura, V. Ashutosh Rao, Olivier Sordet, Takahisa Furuta, Ze-Hong Miao, LingHua Meng, Hongliang Zhang and Yves Pommier. Defective activation of Chk2 by ATM and Mre11 in colorectal carcinoma cells in response to replication-dependent DNA double-strand breaks. J Biol Chem 2006；281:30814-23.

43)Yves Pommier, Juana Barcelo, V. Ashutosh Rao, Olivier Sordet, Andrew G. Jobson, Laurent Thibaut, Ze-Hong Miao, Jennifer Seiler, Hongliang Zhang, Christophe Marchand, Keli Agama and Christophe Redon. Repair of Topoisomerase I-Mediated DNA Damage. Progress In Nucleic Acid Research And Molecular Biology 2006; 81:179-229.

44)Xiangshu Xiao, Ze-Hong Miao, Smitha Antony, Yves Pommier, Mark Cushman. Dihydroindenoisoquinolines function as prodrugs to indenoisoquinolines. Bioorg Med Chem Lett. 2005;15(11):2795-8.

45)Hua-Rui Lu, Hong Zhu, Min Huang, Yi Chen, Yu-Jun Cai, Ze-Hong Miao, Jin-Sheng Zhang, and Jian Ding. Reactive Oxygen Species Elicit Apoptosis by Concurrently Disrupting Topoisomerase II and DNA-dependent Protein Kinase. Mol Pharmacol, 2005; 68: 983-994.

46)Hua-Rui Lu, Ling-Hua Meng, Min Huang, Hong Zhu, Ze-Hong Miao, Jian Ding. DNA Damage, c-myc Expression Suppression and Apoptosis Induced by the Novel Topoisomerase II Inhibitor, Salvicine, in Human Breast Cancer MCF-7 Cells. Cancer Chemother Pharmacol 2005; 55: 286-294.

47)Wei-Jun Liu, Yong-Wei Zhang, Ying Shen, Jian-Fei Jiang, Ze-Hong Miao, Jian Ding. Telomerase inhibition is a specific early event in salvicine-treated human lung adenocarcinoma A549 cells. Biochem Biophys Res Commun 2004; 323: 660-667.

48)Qing Chen, Miao Ze-Hong, Zhang Jin-Sheng, Ding Jian. Actinomycin D inhibiting K562 cell apoptosis elicited by the anti-topoisomerase II agent salvicine, but not decreasing its cytotoxicity. Acta Pharmacol Sin. 2003;24:415-421.

4. On tumor angiogenesis inhibitors

49)Lin Xu, Wei Wang, Tao Meng, Lan-Ping Ma, Lin-Jiang Tong, Jing-Kang Shen, Ying-Qing Wang*, Ze-Hong Miao*. New Microtubulin Inhibitor MT189 Suppresses Angiogenesis by Reducing Endothelial Migration via the JNK-VEGF/VEGFR2 Signaling Axis. Cancer Lett. 2018; 416:57-65.

50)Yan Wang, Jia-Xin Li, Ying-Qing Wang*, Ze-Hong Miao*. Tanshinone I Inhibits Tumor Angiogenesis by Reducing Stat3 Phosphorylation at Tyr705 and Hypoxia-induced HIF-1α Accumulation in both Endothelial and Tumor Cells. Oncotarget. 2015; 6(18):16031-42.

51)Wei Wang, Ying-Qing Wang, Tao Meng, Jun-Mei Yi, Xia-Juan Huan, Lan-Ping Ma, Lin-Jiang Tong, Yi Chen, Jian Ding, Jing-Kang Shen*, Ze-Hong Miao*. MCL-1 Degradation Mediated by JNK Activation via MEKK1/TAK1-MKK4 Contributes to Anticancer Activity of New Tubulin Inhibitor MT189. Mol Cancer Ther. 2014;13(6); 1480-91.

52)Tao Meng, Wei Wang, Zhixiang Zhang, Lanping Ma*, Yongliang Zhang, Zehong Miao*, Jingkang Shen*. Synthesis and biological evaluation of 6H-pyrido[2\',1\':2,3]imidazo[4,5-c]isoquinolin-5(6H)-ones as antimitotic agents and inhibitors of tubulin polymerization. Bioorg Med Chem 2014; 22:848-855.

53)Ying-Qing Wang, Ze-Hong Miao*. Marine-derived angiogenesis inhibitors for cancer therapy. Mar Drugs. 2013;11(3):903-933.

54)Zhao-Li Zhou, Ya-Xi Yang, Jian Ding, Yuan-Chao Li*, Ze-Hong Miao*. Triptolide: structural modifications, structure-activity relationships, bioactivities, clinical development and mechanisms. Nat Prod Rep. 2012; 29(4): 457-475

55)Stefano Giustino Manzo, Zhao-Li Zhou, Ying-Qing Wang, Jessica Marinello, Jin-Xue He, Yuan-Chao Li, Jian Ding, Giovanni Capranico*, Ze-Hong Miao*. Natural product triptolide mediates cancer cell death by triggering CDK7-dependent degradation of RNA polymerase II. Cancer Res. 2012; 72(20): 5363-5373.

56)Ze-Hong Miao*, Jian-Ming Feng, Jian Ding*. Newly discovered angiogenesis inhibitors and their mechanisms of action. Acta Pharmacol Sin. 2012; 33(9): 1103–1111.

57)Bing Yu, Mei-Hong Li, Wei Wang, Ying-Qing Wang, Yi Jiang, Sheng-Ping Yang, Jian-Min Yue, Jian Ding*, Ze-Hong Miao*. Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in stabilizing HIF-1alpha: a novel function-converter model. J Mol Med (Berl). 2012; 90(8):971–981.

58)Zhixiang Zhang, Tao Meng, Na Yang, Wei Wang, Bing Xiong, Yi Chen, Lanping Ma, Jingkang Shen, Ze-Hong Miao*, Jian Ding*. MT119, a new planar-structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation. Int J Cancer 2011; 129(1):214-224.

59)Zhou B, Li X, Tang H, Miao Z, Feng H, Li Y. Total synthesis of novel D-ring-modified triptolide analogues: structure-cytotoxic activity relationship studies on the D-ring of triptolide. Org Biomol Chem. 2011, 9(9):3176-3179.

60)Zhao-Li Zhou, Zhi-Guo Luo, Bing Yu, Yi Jiang, Yi Chen, Jian-Ming Feng, Mei Dai, Lin-Jiang Tong, Zheng Li, Yuan-Chao Li, Jian Ding, Ze-Hong Miao*. Increased accumulation of hypoxia-inducible factor-1α with reduced transcriptional activity mediates the antitumor effect of triptolide. Mol Cancer, 2010;9:268pp1-11.

61)Bing Zhou, Zehong Miao, Gang Deng, Jian Ding, Yaxi Yang, Huijin Feng, Yuanchao Li*. Synthesis and biological evaluation of novel triptolide analogues for anticancer activity. Bioorg Med Chem Lett. 2010; 20(21):6217-6221.

62)Zhixiang Zhang, Tao Meng, Jingxue He, Ming Li, Lin-Jiang Tong, Bing Xiong, Liping Lin, Jingkang Shen, Ze-Hong Miao*, Jian Ding*. MT7, a novel compound from a combinatorial library, arrests mitosis via inhibiting the polymerization of microtubules. Invest New Drug. 2010;28(6):715-728.

63)Mei Dai, Ze-Hong Miao*, Xuan Ren, Lin-Jiang Tong, Na Yang, Ting Li, Li-Ping Lin, Yue-Mao Shen, Jian Ding*. MFTZ-1, a novel topoisomerase II poison, reduces constitutive and inducible HIF-1α accumulation and VEGF secretion irrelevant to its topoisomerase II inhibition. J Cell Mol Med. 2010; 14(9): 2281–2291.

64)Bing Yu, Ze-Hong Miao*, Yi Jiang, Mei-Hong Li, Na Yang, Ting Li, Jian Ding*. c-Jun protects HIF-1α from degradation via its Oxygen-Dependent-Degradation domain in a non-transcriptional manner. Cancer Res. 2009; 69(19):7704-7712.

65)Zheng Li, Zhao-Li Zhou, Ze-Hong Miao, Li-Ping Lin, Hui-Jin Feng, Lin-Jiang Tong, Jian Ding, Yuan-Chao Li*. Design and Synthesis of Novel C14-hydroxyl Substituted Triptolide Derivatives as Potential Selective Antitumor Agents. J Med Chem. 2009, 52(16): 5115–5123.

66)Yi Chen, Yi-Xiang Zhang, Mei-Hong Li, Wei-Min Zhao, Yu-Hua Shi, Ze-Hong Miao, Xiong-Wen Zhang, Li-Ping Lin, Jian Ding*. Antiangiogenic activity of 11,11′-dideoxyverticillin, a natural product isolated from the fungus Shiraia bambusicola. Biochem Biophys Res Commun, 2005; 329 (4):1334-1342.

67)Mei-Hong Li, Ze-Hong Miao, Wen-Fu Tan, Jian-Min Yue, Chao Zhang, Li-Ping Lin, Xiong-Wen Zhang, Jian Ding*. Pseudolarix acid B inhibits angiogenesis and reduces hypoxia-inducible factor-1??by promoting proteosome-mediated degradation. Clin Cancer Res 2004; 10: 8266-8274.

5.On tumor drug resistance

68)Jing-Qiu Li, Xian Wu, Lu Gan, Xiang-Liang Yang*, Ze-Hong Miao*. Hypoxia Induces Universal but Differential Drug Resistance and Impairs Anticancer Mechanisms of 5-Fluorouracil in Hepatoma Cells. Acta Pharmacol Sin. 2017;38: 1642–1654.

69)Jun-Mei Yi, Xia-Juan Huan, Shan-Shan Song, Hu Zhou, Ying-Qing Wang*, Ze-Hong Miao*. Triptolide Induces Cell Killing in Multidrug-Resistant Tumor Cells via CDK7/Rpb1 rather than XPB or p44. Mol Cancer Ther. 2016; 15(7) :1495-1503.

70)Hong Xin, Ying Kong, Xiaoxiao Jiang, Ke Wang, Xiaoran Qin, Ze-Hong Miao, Yizhun Zhu, Wenfu Tan*. Multi-Drug-Resistant Cells Enriched From Chronic Myeloid Leukemia Cells by Doxorubicin Possess Tumor-Initiating-Cell Properties. J Pharmacol Sci. 2013; 122(4):299-304.

71)Yi Jiang, Ze-Hong Miao*, Bing Yu, Lei Xu, Jing-Xu Gong, Lin-Jiang Tong, Yi Chen, Zhao-Li Zhou, Hong-Chun Liu, Yi Wang, Yue-Wei Guo, Jian Ding*. Drug-transporter-independent liver cancer cell killing by a marine steroid methyl spongoate via apoptosis induction. J Biol Chem 2011; 286(30):26461- 26469.

72)Yujun Cai, Jinjian Lu, Zehong Miao, Liping Lin, Jian Ding*. Reactive oxygen species contribute to cell killing and p-glycoprotein downregulation by salvicine in multidrug resistant K562/A02 cells. Cancer Biol Ther 2007; 6: 1794-1779.

73)Ze-Hong Miao, Lin-Jiang Tong, Jin-Sheng Zhang, Jia-Xian Han, Jian Ding*. Characterization of salvicine-resistant lung adenocarcinoma A549/SAL cell line. Int J Cancer 2004; 110: 627–632.

74)Ze-Hong Miao, Jian Ding*. Transcription factor c-Jun activation represses mdr-1 gene expression. Cancer Res 2003; 63: 4527-4532.

75)Ze-Hong Miao, Tao Tang, Yi-Xiang Zhang, Jin-Sheng Zhang, Jian Ding*. Cytotoxicity, apoptosis induction and downregulation of mdr-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant cells. Int J Cancer 2003; 106:108-115.

jyjl:09/2000-07/2003中国科学院上海药物研究所，理学博士