丁健 - 中国医科大学

个人简介

丁健（1953.02.20- ），肿瘤药理学专家，研究员，博士生导师，中国工程院院士，现任中国科学院大学药学院院长，中科院上海药物所学术委员会主任。主要研究成果： 1. 抗肿瘤新药研发创制方面：3个抗肿瘤新药进入临床试验，其中FGFR/VEGFR激酶抑制剂AL-3810在欧洲进行II期、在中国进行I期临床研究：K-001在中国进行针对肝细胞性肝癌的II期临床研究：拓扑异构酶I抑制剂希明替康在中国进行I期临床试验。另有2个候选新药正在申报临床试验，6个候选药物进入临床前系统评价。申请国内外专利150余项，其中申请国际专利13项，中国授权专利40余项。 2. 药物作用机制探索和基础研究方面：系统阐明了一系列抗肿瘤化合物或候选新药的作用机制；阐明了数个药靶相互作用的结构基础与作用模式，发现了pIgR、CXCL12、p27/KIP1、c-Myc等重要肿瘤生物标志物。发表SCI学术杂志240多篇论文，他引4000多次。承担科研项目情况化学创新药物研发体系建设国家重大新药创制—综合性新药研究开发技术大平台建设 2009.1-2010.12；2012.1-2015.12 针对分子靶点的抗肿瘤药物发现及其机理研究国家自然基金创新群体科学基金 2008.1-2010.12；2011.1-2013.12 土槿皮乙酸对新生血管生成和微管抑制作用分子机制的深入研国家自然基金重点项目 2008.1-2011.12 治疗重大疾病创新药物的药效学平台建设上海市科委 2006.11-2008.09 分子靶向抗肿瘤候选新药的研发上海市科委 2007.12-2010.10 癌症预防诊治的转化型研究）中国科学院 2009.07-2011.05 中国药物技术创新战略联盟卫生部产学研联盟 2010.1-2012.12 基于蛋白质结构与功能的药物多靶标作用机制研究中科院重要方向 2011.1-2013.12 免疫稳态失衡在炎癌转化的开关机制-免疫负性调控因子SIRPα 在免疫球蛋白受体pIgR 免疫背叛中的调控重大研究计划2013.1-2016.12 获奖及荣誉国家自然科学奖二等奖（2009）国家自然科学二等奖（2013）国家科技进步二等奖（2003）上海市自然科学一等奖（2项，2007，2010）上海市科技进步一等奖（2003）何梁何利科技进步奖（2008）吴阶平医学研究奖－保罗·杨森药学研究一等奖（2006）上海市十大科技精英（2005）第四届德彪－CCRF一等奖（2001）中科院优秀研究生导师（2004，2005） 2009年中国药学会科学技术奖二等奖（2009年） 2011年“十一五”国家科技计划执行突出贡献奖（2011年）

研究领域

1.抗肿瘤新药的筛选和研究开发:1)激酶抑制剂；2）PI3K/mTOR抑制剂；3)拓扑异构酶抑制剂；4）表观遗传修饰抑制剂。 2. 抗肿瘤药物作用机制研究：1）肿瘤细胞信号转导通路；2）肿瘤分子生物标志物；3）抗肿瘤转移。

近期论文

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1. Shen A, Wang L, Huang M, Sun J, Chen Y, Shen Y, Yang X, Wang X, Ding J*, Geng M. c-Myc Alterations Confer Therapeutic Response and Acquired Resistance to c-Met Inhibitors in MET-Addicted Cancers. Cancer Res. 2015 2. Wang X, Ding J*, Meng L. PI3K isoform-selective inhibitors: next-generation targeted cancer therapies. Acta Pharmacol Sin. 2015 Oct;36(10):1170-6. 3. Chan S, Han K, Qu R, Tong L, Li Y, Zhang Z, Cheng H, Lu X, Patterson A, Smaill J, Ren X, Ding J*, Xie H, Ding K. 2,4-Diarylamino-pyrimidines as kinase inhibitors co-targeting IGF1R and EGFRL858R/T790M. Bioorg Med Chem Lett. 2015 Jul 30. 4. Guo X, Chen X, Tong L, Peng X, Huang M, Liu H, Liu H, Ding J*. DCLAK11, a multi-tyrosine kinase inhibitor, exhibits potent antitumor and antiangiogenic activity in vitro. Acta Pharmacol Sin. 2015 Jun 1. doi: 10.1038/aps.2015.25. 5. Zhang J, He P, Xi Y, Geng M, Chen Y, Ding J*. Down-regulation of G9a triggers DNA damage response and inhibits colorectal cancer cells proliferation. Oncotarget. 2015; 20;6(5):2917-27. 6. Song Z, Yang Y, Liu Z, Peng X, Guo J, Yang X, Ai J, Ding J*, Geng M, Zhang A. Discovery of Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent Inhibitory Activities against both Wild-type and Mutant ALK Kinases. J Med Chem. 2015, 8;58(1):197-211. 7. He P, Zhang J, Che YS, He Q, Chen Y, Ding J*. G226, a new ETP derivative, triggers DNA damage, and apoptosis via ROS generation. Acta Pharmacol Sin. 2014 Dec;35(12):1546-55 8. He PX, Che Y, He QJ, Chen Y, Ding J*. G226, a novel epipolythiodioxopiperazine derivative, induces autophagy and caspase-dependent apoptosis in human breast cancer cells in vitro. Acta Pharmacol Sin. 2014;35:1055-64 9. Li X, Tong L, Ding J*, Meng L. Systematic combination screening reveals synergism between rapamycin and sunitinib against human lung cancer. Cancer Lett. 2014 , 342(1):159-66. 10. Huang X, Sun D, Pan Q, Wen W, Chen Y, Xin X, Huang M, Ding J*, Geng M. JG6, a novel marine-derived oligosaccharide, suppresses breast cancer metastasis via binding to cofilin. Oncotarget. 2014;5(11):3568-78. 11. Liu J, Gao G, Zhang X, Cao S, Guo C, Wang X, Tong L, Ding J*, Duan W, Meng L. DW09849, a Selective Phosphatidylinositol 3-Kinase (PI3K) Inhibitor, Prevents PI3K Signaling and Preferentially Inhibits Proliferation of Cells Containing the Oncogenic Mutation p110α (H1047R). J Pharmacol Exp Ther. 2014;348(3):432-41. 2014 12. Chen S, Guo C, Shi J, Xu Y, Chen Y, Shen Y, Su Y, Ding J*, Meng L. HSP90 inhibitor AUY922 abrogates up-regulation of RTKs by mTOR inhibitor AZD8055 and potentiates its antiproliferative activity in human breast cancer. Int J Cancer. 2014;135(10):2462-74 13. Ji X, Peng T, Zhang X, Li J, Yang W, Tong L, Qu R, Jiang H, Ding J*, Xie H, Liu H. Design, synthesis and biological evaluation of novel 6-alkenylamides substituted of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor receptor inhibitors. Bioorganic & Medicinal Chemistry, 22(7), 2014, 2366–2378. 2014 14. Liu L, Han K, Chen W, Zhang Y, Tong L, Peng T, Xie H, Ding J*, Wang H. Topoisomerase II inhibitors from the roots of Stellera chamaejasme L. Bioorg Med Chem. 2014 (14)00400-3. 15. Wang L, Ai J, Shen Y, Zhag H, Peng X, Huang M, Zhang A, Ding J*, Geng M. SOMCL-863, a novel, selective and orally bioavailable small-molecule c-Met inhibitor, exhibits antitumor activity both in vitro and in vivo. Cancer Lett. 2014 (14)269-9. 16. Xu Y, Han K, Li Q, Tong L, Yang Y, Chen Zh*, Xie H*, Ding J*, Qian X, Xu Y. Novel metal complexes of naphthalimideecyclam conjugates as potential multi-target receptor tyrosine kinase (RTK) inhibitors: Synthesis and biological evaluation. Eur J Med Chem. 2014;85:207-14. 17. Peng T, Wu J, Tong L, Li M, Chen F, Leng Y, Qu R, Han K, Su Y, Chen Y, Duan W, Xie H, Ding J*. Identification of DW532 as a novel anti-tumor agent targeting both kinases and tubulin. Acta Pharmacol Sin. 2014 ;35(7):916-28. 18. He CX, Ai J, Xing WQ, Chen Y, Zhang HT, Huang M, Hu YH, Ding J*, Geng MY. Yhhu3813 is a novel selective inhibitor of c-Met Kinase that inhibits c-Met-dependent neoplastic phenotypes of human cancer cells. Acta Pharmacol Sin. 2014;35(1):89-97. 19. Huang M, Shen A, Ding J*, Geng M, Molecularly targeted cancer therapy: some lessons from the past decade. Trends Pharmacol Sci.2014;35(1):41-50. 20. Wang X, Zhang X, Li BS, Zhai X, Yang Z, Ding LX, Wang H, Liang C, Zhu W, Ding J*, Meng L. Simultaneous targeting of PI3Kδ and a PI3Kδ-dependent MEK1/2-Erk1/2 pathway for therapy in pediatric B-cell acute lymphoblastic leukemia. Oncotarget. 2014 Nov 15;5(21):10732-44. 21. Zhao Y, Zhang X, Chen Y, Lu S, Peng Y, Wang X, Guo C, Zhou A, Zhang J, Luo Y, Shen Q, Ding J*, Meng L, Zhang J. Crystal Structures of PI3Kα Complexed with PI103 and Its Derivatives: New Directions for Inhibitors Design. ACS Med Chem Lett. 2013;5(2):138-42. 22. Huang X, Pan Q, Sun D, Chen W, Shen A, Huang M, Ding J*, Geng M. O-GlcNAcylation of cofilin promotes breast cancer cell invasion. J Biol Chem. 2013; 288(51):36418-25. 2013. 23. Wang X, Li JP, Yang Y, Ding J*, Meng L. A pharmacological model reveals biased dependency on PI3K isoforms for tumor cell growth. Acta Pharmacol Sin. 34: 1201–1207, 2013. 24. Wen W, Xie S, Xin X, Geng M, Ding J*, Chen Y.Oligomannurarate sulfate inhibits CXCL12/SDF-1-mediated proliferation and invasion of human tumor cells in vitro. Acta Pharmacol Sin. 2013;34(12):1554-9. 2013 25. Dong S, Liu J, Ge Y, Dong L, Xu C, Ding J*, Yue J. Chemical constituents from Brucea javanica. Phytochemistry.2013;85:175-84. 2013 26. Wang X, Chen Z, Tong L, Tan S, Zhou W, Peng T, Han K, Ding J*, Xie H, Xu Y. Naphthalimides exhibit in vitro antiproliferative and antiangiogenic activities by inhibiting both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs). Eur J Med Chem. 2013;65:477-86. 2013 27. Zhang J, Xin X, Chen Q, Xie Z, Gui M, Chen Y, Lin LP, Feng JM, Li QN, Ding J*, Geng M*. Oligomannurarate sulfate sensitizes cancer cells to doxorubicin by inhibiting atypical activation of NF-kappaB via targeting of Mre11. Int J Cancer. 130: 467-477, 2012 . 28. Wang J, Wang X, Chen Y, Chen S，Chen G，Tong L, Meng L, Xie Y, Ding J*, and Yang C. Discovery and bioactivity of 4-(2-arylpyrido[3',2':3,4]pyrrolo [1,2-f][1,2,4] triazin-4-yl) morpholine derivatives as novel PI3K inhibitors. Bioorg. Med. Chem. Lett. 22(1):339-42, 2012 . 29. Chen G, Chen S, Wang X, Ding X, Ding J*, Meng L. Inhibition of Chemokine (CXC Motif) Ligand 12/Chemokine (CXC Motif) Receptor 4 Axis CXCL12/CXCR4)-mediated Cell Migration by Targeting Mammalian Target of Rapamycin (mTOR) Pathway in Human Gastric Carcinoma Cells. J Biol Chem. 287(15):12132-41, 2012 . 30. Chen S, Liu JL, Wang X, Liang C, Ding J*, Meng L. Inhibition of tumor cell growth, proliferation and migration by X-387, a novel active-site inhibitor of mTOR. Biochem Pharmacol. 83(9):1183-94, 2012. 31. Yu B, Li MH, Wang W, Wang YQ, Jiang Y, Yang SP, Yue JM, Ding J*, Miao Z. Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in stabilizing HIF-1alpha: a novel function-converter model. J Mol Med (Berl). 90(8):971-81, 2012. 32. Zhou Y, Chen Y, Tong L, Xie H, Wen W, Zhang J, Xi Y, Shen Y, Geng M, Wang Y, Jiang H, Luo C, Lin L*, Ding J*. AL3810, a multi-tyrosine kinase inhibitor, exhibits potent anti-angiogenic and antitumor activity via targeting VEGFR, FGFR, and PDGFR. J Cell Mol Med. 16(10):2321-2330, 2012. 33. Feng JM, Miao ZH, Jiang Y, Chen Y, Li JX, Tong LJ, Zhang J, Huang YR, Ding J*.Characterization of the conversion between CD133 (+) and CD133 (-) cells in colon cancer SW620 cell line. Cancer Biol Ther. 13(14):1396-1406, 2012. 34. Miao ZH, Feng JM, Ding J*. Newly discovered angiogenesis inhibitors and their mechanisms of action. Acta Pharmacol Sin. 33(9):1103-11, 2012.. 35. Wang S, Huang X, Sun D, Xin X, Pan Q, Peng S, Liang Z, Luo C, Yang Y, Jiang H, Huang M, Chai W, Ding J*, Geng M. Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates Akt signaling. PLoS One. 7(5):e37427, 2012. 36. Lu JJ, Chen SM, Ding J*, Meng LH.Characterization of dihydroartemisinin-resistant colon carcinoma HCT116/R cell line. Mol Cell Biochem. 360(1-2):329-37, 2012. 37. Lu J, Cai YJ, Ding J*.The short-time treatment with curcumin sufficiently decreases cell viability, induces apoptosis and copper enhances these effects in multidrug-resistant K562/A02 cells. Mol Cell Biochem. 360(1-2):253-60, 2012. 38. Lu J, Chen SM, Zhang XW, Ding J*, Meng LH*. The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest New Drugs. 29:1276-1283, 2011. 39. Zhang Z, Meng T, Yang N, Wang W, Xiong,B, Chen Y, Ma L, Shen J, Miao Z*, Ding J*. MT119, a new planar-structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation. Int J Cancer. 129:214-224, 2011. 40. Zhu C, Chen Q, Xie Z, Ai J, Tong L, Ding J*, Geng M*. The role of histone deacetylase 7 (HDAC7) in cancer cell proliferation: regulation on c-Myc. J Mol Med. 89(3):279-89, 2011. 41. Tong L, Xie H, Peng T, Liu XF, Xin XL, Huang X, Chen SM, Liu HY, Li HL, Geng MY, Yin M*, Ding J*. Establishment of platform for screening insulin-like growth factor-1 receptor inhibitors and evaluation of novel inhibitors. Acta Pharmacol Sin. 1:1-9, 2011. 42. Jiang Y, Miao Z, Xu L, Yu B, Gong J, Tong J, Chen Y, Zhou L, Liu C, Wang Y, Guo W, Ding J*. Drug transporter-independent liver cancer cell killing by a marine steroid methyl spongoate via apoptosis induction. J Biol Chem. 286(30): 26461 -69, 2011. 43. Gui M, Shi D, Huang M, Zhao Y, Sun Q, Zhang J, Chen Q, Feng J, Liu C, Li M, Li Y, Geng M., Ding J*. D11, a novel glycosylated diphyllin derivative, exhibits potent anticancer activity by targeting topoisomerase IIalpha. Invest New Drugs. 29(5):800-810, 2011. 44. Lu J, Cai Y, Ding J*. Curcumin induces DNA damage and caffeine-insensitive cell cycle arrest in colorectal carcinoma HCT116 cells. Mol Cell Biochem. 354(1-2): 247-52, 2011. 45. Xie H, Lin L, Tong L, Jiang Y, Zheng M, Chen Z, Jiang X, Zhang X, Ren X, Qu W, Yang Y, Wan H, Chen Y, Zuo J, Jiang H, Geng M, and Ding J*. AST1306, A Novel Irreversible Inhibitor of the Epidermal Growth Factor Receptor 1 and 2, Exhibits Antitumor Activity Both In Vitro and In Vivo. PLoS One, 6(7): p. e21487, 2011. 46. Ai J, Tang Q, Wu Y, Xu Y, Feng T, Zhou R, Gao X, Zhu Q, Yue X, Pan Q, Xu S, Li J, Huang M, Daugherty-Holtrop, J, He Y, Xu H, Fan J, Ding J*, Geng M. The Role of Polymeric Immunoglobulin Receptor in Inflammation-Induced Tumor Metastasis of Human Hepatocellular Carcinoma. J Natl Cancer Inst. 103(22):1696-712, 2011. 47. Chen Z, Wang X, Zhu W, Cao X, Tong L, Li H, Xie H, Xu Y, Tan H, Kuang D, Ding J*, Qian X. Acenaphtho[1,2-b]pyrrole-based selective fibroblast growth factor receptors 1 (FGFR1) inhibitors: design, synthesis, and biological activity. J Med Chem. 54(11):3732-45, 2011. 48. Dong S, Zhang C, Xu C, Ding J*, Yue J. Daphnane-Type Diterpenoids from Trigonostemon howii. J Nat Prod. 74(5):1255-61, 2011. 49. Wang Y, Li X, He Q, Chen Y, Xie Y, Ding J*, Miao Z, Yang CH*. Design, synthesis and biological evaluation of substituted 11H-benzo[a]carbazole-5 -carboxamides as novel antitumor agents. Eur J Med Chem. 46(12):5878-84, 2011. 50. Chen S, Meng L, Ding J*. New microtubule-inhibiting anticancer agents. Expert Opin Inv Drug 19: 329-343, 2010. 51. Lu J, Meng L, Shankavaramb UT, Zhu C, Tong L, Chen G, Lin L, Weinsteinc J, Ding J*. Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells. Biochem Pharmacol 80: 22-30, 2010. 52. Dai M, Miao Z, Ren X, Tong L, Yang N, Li T, Lin L, Shen Y, Ding J*. MFTZ-1 reduces constitutive and inducible HIF-1alpha accumulation and VEGF secretion independent of its topoisomerase II inhibition. J Cell Mol Med. 10: 2281-2291, 2010. 53. Zhang Z, Meng T, He J, Li M, Tong LJ, Xiong B, Lin L, Shen J, Miao Z, Ding J*. MT7, a novel compound from a combinatorial library, arrests mitosis via inhibiting the polymerization of microtubules. Invest New Drugs. 28: 715-728, 2010. 54. Li M, Miao Z, Chen Z, Chen Q, Gui M, Lin LP, Sun P, Yi YH, Ding J*. Echinoside A, a new marine-derived anticancer saponin, targets topoisomerase II by unique interference with its DNA binding and catalytic cycle. Ann Oncol. 21: 597-607, 2010. 55. Li T, Wang J, Wang X, Yang N, Chen SM, Tong LJ, Yang CH, Meng L, Ding J*. WJD008, a dual phosphatidylinositol 3-Kinase (PI3K)/mammalian target of rapamycin inhibitor, prevents PI3K signaling and inhibits the proliferation of transformed cells with oncogenic PI3K mutant. J Pharmacol Exp Ther. 334: 830-838, 2010. 56. Chen G, Yang N, Wang X, Zheng SY, Chen Y, Tong LJ, LI YX, Meng L, Ding J*. Identification of p27/KIP1 expression level as a candidate biomarker of response to rapalogs therapy in human cancer. J Mol Med. 88: 941-952, 2010. 57. Zhou ZL, Luo ZG, Yu B, Jiang Y, Chen Y, Feng JM, Dai M, Tong LJ, Li Z, Li Y, Ding J*, Miao ZH. Increased accumulation of hypoxia-inducible factor-1α with reduced transcriptional activity mediates the antitumor effect of triptolide. Mol Cancer. 9:268, 2010. 58. Zhang J, Chen Y, Xin XL, Li QN, Li M, Lin LP, Geng M, Ding J*. Oligomannurarate sulfate blocks tumor growth by inhibiting NF-kappaB activation. Acta Pharmacol Sin 31: 375-381, 2010. 59. Chen G, Hao XJ, Sun QY, Ding J*. Rapid synthesis and bioactivities of 3-(nitromethylene)indolin-2-one analogues. Chememical Papers, 64:673-677, 2010. 60. Lu D, Lu DR, Ding J*, Cell Biological Manifestations of Bisdioxopiperazines: Treatment of Human Tumor Cell Lines in Culture. Anticancer Agents Med Chem, 10:657-660,2010. 61. Chen S, Liu JL, Wang X, Liang C, Ding J* , Meng L, Novel pyrazolopyrimidine derivatives as potent mTOR kinase inhibitors with anticancer activities. Biochem Pharmacol, 8:54-54, 2010

学术兼职

兼任中国抗癌协会、中国药学会和中国药理学会的常务理事；中国抗癌协会抗癌药物专业委员会、中国药理学会肿瘤药理专业委员会的主任委员。担任Acta Pharmacol Sin 主编和J Biol Chem、Eur J Pharmacol、Cancer Biol Ther、J Ethnopharmacol 和Molecular Pharmacology等SCI学术杂志编委。