丁克 男 汉族 博导 广州生物医药与健康研究院

电子邮件：ding_ke@gibh.ac.cn
联系电话：**
通信地址：广州市萝岗区开源大道190号
邮政编码：510530


研究领域药物化学：主要方向为抗肿瘤药物、抗病毒药物、代谢疾病药物的设计与合成

教育背景

学历1995年9月~ 1998年7月 药物化学硕士，中国药科大学

1998年9月~ 2001年7月 生物有机化学博士，复旦大学化学系与中国科学院上海有机化学研究所联合培养

出国学习工作 2001年12月~ 2005年2月 博士后研究，美国密西根大学肿瘤中心（the University of Michigan，Ann Arbor）

2005年3月~ 2006年3月 Research Investigator (研究型Faculty), 美国密西根大学医学院
工作经历

工作简历 丁克博士，中科院广州生物医药与健康研究院研究员，博士生导师。2005年3月任美国密西根大学医学院Research Inivestigator。2006年3月回国加入中科院广州生物医药与健康研究院， 2007年入选“中国科学院百人计划”。2008年入选广州市优秀专家。2009年获“广东省丁颖科技奖”。现任中科院广州生物医药与健康研究院研究员，中科院广州生物医药与健康研究院化学生物所副所长。
丁克博士的研究工作主要集中在新型抗肿瘤药物、治疗代谢性疾病药物等具有重要生物活性的小分子调节剂的设计和合成，为新药开发提供先导化合物。成功设计合成了：1）Spirooxindole类MDM2抑制剂(以3.98亿美元转让Sanifi-Aventis)；2）异黄酮类Bcl-2抑制剂(转让美国Ascenta，其中AT-101已进入II期临床)；3）世界首个选择性ERRa激动剂；4）可有效克服格列卫临床耐受的全新蛋白激酶抑制剂等；5）首次发现了niclosamide为全新的STAT3抑制剂；6）开发了quinazolinone，取代吲哚，取代indazole等的高效合成方法。在J. Am. Chem. Soc.; J. Med. Chem.；ACS Med. Chem. Lett.等发表论文43篇，他引550余次，单篇最高110次。申请发明专利20项，授权5项。2010年任ACS Med. Chem. Lett.顾问编委。 指导在读博士研究生8名，指导硕士研究生5名（其中1名已获得学位）。

社会兼职2010- 美国ACS Medicinal Chemistry Letter (原J. Med. Chem. 的Letter部分)杂志，顾问编委 （Advisory Editorial Board Member）；
2009- 广东省药学会药物化学专业委员会，副主任委员；
2009.07-2014.07 广州市青年联合会第十一届委员会委员;
2009.02-2011.02广东省青年科学家协会，第三届会员，理事;
2006- 中国药学会，高级会员；
2004- 北美华人生物学家协会（CBA）会员；
2002- 美国化学会（ACS），会员。
J. Med. Chem.; Chem. Comm.; Eur. J. Med. Chem.; Tetrah. Lett.; Bioorg. Med. Lett. 等国际学术刊物审稿人。

教授课程文献综述（药化类） 2007—2008学年秋季学期

文献综述（药化类） 2010—2011学年秋季学期

专利成果申请专利情况：共申请专利22项，其中授权4项；PCT5项。其中第一发明人或除导师外第一发明人20项。

授权专利：
1. Ma, Dawei; Ding, Ke; Wu, Wengen; Li, Jia. Preparation of 2-arylsulfonyltetrahydroisoquinoline hydroximic acid derivs. as matrix metalloproteinase inhibitors.中国发明专利 授权号CN **C
2．Ma, Dawei; Ding, Ke; Ye, Qizhuang; Li, Jia. Preparation of alkynylaryloxoalkanoates as matrix metalloproteinase inhibitors. 中国发明专利 授权号CN **C
3.丁克，王德平 2－吡啶－bata酮类化合物的应用。中国发明专利，专利号： **7.5。
4.丁克，王广军，张虎山，周净 化合物ABT-263的合成方法。中国发明专利，专利号：**0.0。
PCT申请及进入国外阶段申请情况（5项）：
1． Wang, Shaomeng; Ding, Ke; Tang, Guozhi; Wang, Renxiao; Yang, Chao-Yie; Nikolovska-Coleska, Zaneta. Preparation of chromen-4-ones as inhibitors of anti-apoptotic BCL-2 family members for treatment of cancer. PCT Int. Appl. (2006), 92pp. WO **.
2． Wang, Shaomeng; Ding, Ke; Lu, Yipin; Nikolovska-Coleska, Zaneta; Qiu, Su; Wang, Guoping; Qin, Dongguang; Shangary, Sanjeev. Preparation of spirotryprostatin A derivatives as inhibitors of MDM2. PCT Int. Appl. (2006), 216pp. WO **。
3. Wang, Shaomeng; Varady, Judith; Wu, Xihan; Min, Ji; Ding, Ke; Levant, Beth. Preparation and evaluation of fused pyrazinoquinolines as dopamine receptor ligands. PCT Int. Appl. (2002), 136 pp. WO **。
4．丁克，黄志伟 用作雌激素相关受体调节剂的化合物及其应用。中国发明专利，申请号 **2.0。The compounds as the estrogen related receptors modulators and the uses thereof PCT申请PCT/CN2009/000234，国际公布号：WO**。美国申请号：US 12/879,415, 欧洲申请号EP：**.7 日本申请号：2010-550017
5．丁克，黄志伟, 彭丽洁 雌激素相关受体调节剂及其应用。The compounds as the estrogen related receptors modulators and the uses thereof中国发明专利，申请号 **6.9。PCT申请PCT/CN2009/000243，国际公布号：WO**。.
其它专利申请：
1．丁克，裴端卿，段磊，任小梅，吕满，万晓祯，张章，何蔷 化合物氯硝柳胺及其药学上可接受的盐在制备抗肿瘤药物中的应用。中国发明专利，申请号 **6.8。
2．丁克，裴端卿，王德平，段磊，任小梅，周净，甘继荣，周凤涛，张章 二芳基脲类化合物及其在抗肿瘤药物制备中的应用。中国发明专利，申请号 **4.4。
3．丁克，裴端卿，李正伟，任小梅，段磊，何蔷，张章 Jak-STAT3信号通路抑制剂及其在制备抗肿瘤药物中的应用。中国发明专利，申请号 **4.X。
4. 丁克，裴端卿，周净 氯硝柳胺磷酸酯、其药学上可接受的盐及其应用。中国发明专利，申请号 **3.X。
5．丁克, 王德平, 裴端卿, 潘景轩, 张章, 冯玉冰, 罗坤, 甘继荣, 庄晓曦, 段磊. 吡啶基噻唑胺类化合物及其应用.中国发明专利，申请号 **1.0。
6. 丁克 刘秀洁，王东业，惠晓艳，徐爱民，吴东海. 一种吡唑类化合物及其组合物和应用. 中国发明专利，申请号**0.5.
7. 丁克 常少华 吴东海 周毅 .一种新型PAMAM的衍生物及其应用中国发明专利，申请号**20
8. 丁克 李正球，蔡倩. 一种喹啉、吲哚衍生物的合成方法. 中国发明专利，申请号**7.1.
9．丁克，黄志伟 用作雌激素相关受体调节剂的化合物及其应用。中国发明专利，申请号 **2.0。
10．丁克，黄志伟, 彭丽洁 雌激素相关受体调节剂及其应用。中国发明专利，申请号 **6.9。
11．丁克，王德平，裴端卿，张章，沈梦婕，罗坤，冯玉冰 杂环炔苯类化合物及其药用组合物和应用。中国发明专利，申请号 **3.7
12. 丁克 周凤涛 蔡倩. 一种含有二氢茚酮并吡咯骨架的化合物的合成方法. 中国发明专利，申请号**.7.
13.朱孝峰 丁克 邓蓉 常少华. 5-噻唑酰胺类化合物及其生物学应用. 中国发明专利，申请号**5.5（合作单位：中山大学肿瘤防治中心）

论文发表情况总计发表45篇SCI论文，其中第一作者8篇，通讯作者20篇

1. Chen, Jiekai, Liu, Jing, Yang, Jiaqi, Chen, You, Chen, Jing, Ni, Su, Song, Hong, Zeng, Lingwen, Ding, Ke, Pei, Duanqing. BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone. CELL RESEARCH, 21(1), pp 205-212, 2011/1(SCIE).
2. Xiaomei Ren, Qiang He; Lei Duan, Zhang Zhang, Yi Zhou, Donghai Wu, Jingxuan Pan, Duanqing Pei and Ke Ding * Identification of a New Small-Molecule Inhibitor of STAT3 Signaling Pathway. ACS Med. Chem. Lett.（原J. Med. Chem. 快报部分）2010, 1 (9), 454–459.（IF：4.9）
3. Jin Zhang, Jing Zhou, Xiaomei Ren, Honglin Li, Huangliang Jiang, Ke Ding * and Duanqing Pei A new diaryl urea compound, D181, induces cell cycle arrest in the G1 and M phases by targeting receptor tyrosin kinases and the microtubule skeleton. Investigational New Drugs (2010) DOI 10.1007/s10637-010-9577-1.（IF：3.43）
4. Cai, Qian; Zhou, Fengtao; Xu, Tianfeng; Fu, liangbing, Ding, Ke*. Copper-Catalyzed Tandem Reactions of 1-(2-Iodoary) -2-yn-1-ones with Isocyanides for the Synthesis of 4-Oxo-indeno[1,2-b]pyrroles. Organic Lett. 2010-02826f (IF = 5.4)
5. Zhengqiu Lia,b, Liangbin Fub,c, Jiajia Weic, Chengyong Haa, Duanqing Peic, Qian Cai*c, Ke Ding*c A Room-Temperature, Copper-Catalyzed Cascade Process for Diethyl 2-Aryl-3,4-dihydro-4-oxo-1,1(2H)-naphthalenedicarboxylate.Synthesis,2010 DOI: 10.1055/s-**(IF = 2.47)
6. Cai, Qian; Wei, Jiajia; Fu, Liangbin; Pei, Duanqing and Ding，Ke* Synthesis of Aza-Fused Polycyclic Quinolines through Copper-Catalyzed Cascade Reactions. Organic Lett. 2010，12（7），1500-1503 (IF = 5.13) 通讯作者。
7. Huaming Chen, Deping Wang, Xianyang Wang, Wenlong Huang, Qian Cai, Ke Ding*
Mild Conditions for Copper-Catalyzed N-Arylation of Imidazoles. SYNTHESIS, 2010(9): 1505-1511 (IF = 2.47) 通讯作者。
8.Yanli Jin, Zhongzheng Lu, Ke Ding, Juan Li, Xin Du, Chun Chen, Xiaoyong Sun, Yongbin Wu, Jing Zhou, and Jingxuan Pan Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem Cells: Inactivation of the NF- B Pathway and Generation of Reactive Oxygen Species。Cancer Res. 2010 70: 2516-2527。(IF = 7.543)
9.Xiaoyan Hui, Huiying Li, Zhiguang Zhou, Karen S L Lam1, , Yang Xiao, Donghai Wu, Ke Ding, Yu Wang, Paul M. Vanhoutte, Aimin Xu. Adipocyte Fatty Acid Binding Protein Modulates Inflammatory Responses in Macrophages through a Positive Feedback Loop Involving C-Jun N-terminal kinases and Activator Protein-1. J. Bio. Chem. (2010), 285,10273-10280(IF = 5.52)
10. Xianping Shi, Deping Wang, Ke Ding, Zhongzheng Lu, Yanli Jin, Jin Zhang and Jingxuan Pan.eGDP366, a novel small molecule dual inhibitor of survivin and Op18, induces cell growth inhibition, cellular senescence and mitotic catastrophe in human cancer cells. Cancer Biolo&Therapy.2010,9(8),640-650. 11. Deping Wang, Qian Cai and Ke Ding * An Efficient Cu-Catalyzed Amination of Aryl Halides by Aqueous Ammonia. Advanced Synthesis and Catalyst (2009), 351, 1722-1726. (IF = 5.62). *通讯作者
12.Deping Wang and Ke Ding* 2-Pyridinyl beta-Ketones as New Ligands for Room-Temperature CuI-Catalysed C-N Coupling Reactions Chemical Communications (2009), 1891-1893. (IF = 5.34) 通讯作者
13. Qian Cai, Zhengqiu Li, Jiajia Wei, Chengyong Ha, Duanqing Pei and Ke Ding*. Assembly of indole-2-carboxylic acid esters through a ligand-free copper-catalysed cascade process. Chem. Commun., (2009), 48, 7581-7583. (IF = 5.34) 通讯作者
14. Qi Zhang, Deping Wang, Xianyang Wang and Ke Ding * (2-Pyridyl) acetone Promoted Cu-Catalyzed O-arylation of Phenols with Aryl Iodides, Bromides and chlorides. J. Org. Chem. (2009), 74, 7187-7190. (IF = 3.95). 通讯作者
15. Jing Zhou，Lei Duan, Huaming Chen, Xiaomei Ren, Zhang Zhang, Fengtao Zhou, Jinsong Liu , Duanqing Pei and Ke Ding* Atovaquone Derivatives as Potent Cytotoxic and Apoptosis Inducing Agents. Bioorg. Med. Chem. Letts. (2009), 19, 5091-5094. (IF = 2.58). 通讯作者
16.Shanghai Yu, Dongguang Qin, Sanjeev Shangary, Jianyong Chen, Guoping Wang, Ke Ding, Donna McEachern, Su Qiu, Zaneta Nikolovska-Coleska, Rebecca Miller, Sanmao Kang, Dajun Yang, and Shaomeng Wang. Potent and Orally Active Small-Molecule Inhibitors of the MDM2-p53 Interaction. J. Med. Chem. (2009), 7970-7973. (IF = 4.90)
17.Canner, J. A.; Sobo, M.; Ball, S.; Hutzen, B.; DeAngelis, S.; Willis, W.); Studebaker, A. W.; Ding, K.; Wang, S.; Yang, D..; Lin, J. MI-63: A novel small-molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53 BRITISH J. CANCER (2009), 101,774-781. (IF = 4.85).
18. Sun, Steven H., Zheng, Min, Ding, Ke, Wang, Shaomeng, Sun, Yi. A small molecule that disrupts Mdm2-p53 binding activates p53, induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer Biology & Therapy, 7(6), pp 845-852, 2008/6(SCIE).
19. Wang, Deping; Kuang, Liping; Li, Zhengwei; Ding, Ke*. L-proline Promotes Rosenmund-Von Braun Reaction. SynLett (2008), (1), 69-72. (IF = 2.83) 通讯作者
20. Wang,G.; Zhang, H.; Zhou, J.; Ha, C.; Pei, D. and Ding, K*. An Efficient Synthesis of ABT-263, a Novel Inhibitor of Anti-apoptotic Bcl-2 Proteins. SYNTHESIS (2008), 15, 2398 - 2404. (IF = 2.47) 通讯作者
21. Jing Zhou, Liangbing Fu, Man Lv, Jinsong Liu, Duanqing Pei and Ke Ding ？ Ligand Free CuI-Catalyzed Domino Process to Quinazolin-4(3H)-ones. SYNTHESIS (2008), 3974-3980. (IF = 2.47) 通讯作者
22. Wang, G.; Li, Z.; Ha, C.; Ding, K*. Direct oxidation of N-benzylamides to aldehydes or ketones by N-bromosuccinimide. Synthetic Communications (2008), 38 (10), 1629-1637. (IF = 0.98) 通讯作者
23. Shangary, S.; Qin, D.; McEachern, D.; Liu, M.; Miller, R. S.; Qiu, S.; Nikolovska-Coleska, Z.; Ding, K.; Wang, G.; Chen, J.; Bernard, D.; Zhang, J.; Lu, Y.; Gu, Q.; Shah, R. B.; Pienta, K. J.; Ling, X.; Kang, S.; Guo, M.; Sun, Y.; Yang, D.; Wang, S. Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proceedings of the National Academy of Sciences of the United States of America (2008), 105(10), 3933-3938. (IF = 9.38)
24.Shangary, S.; Ding, K.; Qiu, S.; Nikolovska-Coleska, Z.; Bauer, J. A.; Liu, M.; Wang, G.; Lu, Y.; McEachern, D.; Bernard, D.; Bradford, C. R.; Carey, T. E.; Wang, S. Reactivation of p53 by a specific MDM2 antagonist (MI-43) leads to p21-mediated cell cycle arrest and selective cell death in colon cancer. Molecular Cancer Therapeutics (2008), 7(6), 1533-1542. (IF = 5.00)
25.Jiang, Sheng; Li, Zheng; Ding, Ke; Roller, Peter P. Recent progress of synthetic studies to peptide and peptidomimetic cyclization Current Organic Chemistry (2008), 12(17), 1502-1542。(IF = 3.18)
26. Sun SH, Zheng M, Ding K, Wang S, Sun Y. A small molecule that disrupts Mdm2-p53 binding activates p53, induces apoptosis, and sensitizes lung cancer cells to chemotherapy. Cancer Biol Ther. (2008), 7(6), 845 – 852. (IF = 2.76)
27. Kuang, Liping; Zhou, Jing; Chen, Sheng; Ding, Ke*. Room-Temperature Debenzylation of N-Benzylcarboxamides by N-Bromosuccinimide. Synthesis (2007) 3129 - 3134. (IF = 2.47) 通讯作者.
28. G. Tang, K. Ding, Z. Nikolovska-Coleska, C.-Y. Yang, S. Qiu, S. Shangary, R. Wang, J. Guo, W. Gao, J. Meagher, J. Stuckey, K. Krajewski, S. Jiang, P. P. Roller, and S. Wang. Structure-Based Design of Flavonoid Compounds As a New Class of Small-Molecule Inhibitors of the Anti-apoptotic Bcl-2 Proteins. J. Med. Chem. (2007), 50(14), 3163-3166. (IF = 4.90)
29. Zhang M, Ling Y, Yang CY, Liu H, Wang R, Wu X, Ding K, Zhu F, Griffith BN, Mohammad RM, Wang S, Yang D. A novel Bcl-2 small molecule inhibitor 4-(3-methoxy-phenylsulfannyl) -7-nitro-benzo furazan-3-oxide (MNB)–induced apoptosis in leukemia cells. Ann Hematol. (2007), 86(7): 471-81. (IF = 2.45) 30. Ke Ding, Yipin Lu, Zaneta Nikolovska-Coleska, Guoping Wang, Su Qiu, Sanjeev Shangary, Wei Gao, Dongguang Qin, Jeanne Stuckey, Krzysztof Krajewski# Peter P. Roller, and Shaomeng Wang Structure-Based Design of Spiro-oxindoles as Potent, Specific Small-Molecule Inhibitors of the MDM2-p53 Interaction. J. Med. Chem. (2006), 49, 3432-3435. J. Med. Chem. 杂志2006 年4~6月下载率最高的论文之一（Most-Accessed Articles）。并被选为 J. Med. Chem. 杂志 2007年1~6月份期刊的封面文章。(IF = 4.90)
31. Dawei Ma, Yongwen Jiang, Fangping Chen, Li-Kun Gong, Ke Ding, Yong Xu, Renxiao Wang, Aihua Ge, Jin Ren, Jingya Li, Jia Li and Qizhuang Ye. Selective Inhibiton of Matrix Metalloproteinase Isozyme and In Vivo Protection SAainst Emphysema by Substituteb γ-Keto Carboxylic Acids. J. Med. Chem (2006), 49, 456-458. (IF = 4.90)
32. Jianyong Chen, Ke Ding, Beth Levant and Shaomeng Wang. Design of Novel Hexahydropyrazinoquinoline as potent and selective dopamine D3 receptor with improved solubility. Bioorg. & Med.Chem. Letts (2006) 16, 443-446. (IF = 2.53)
33. Ke Ding, Yipin Lu, Zaneta Nikolovska-Coleska, Su Qiu, Yousong Ding, Jeanne Stuckey, Peter P. Roller, York Tomita, Jeffrey R. Deschamps and Shaomeng Wang. Structure-Based Design of Potent and Non-Peptide Small-Molecule Inhibitors of the p53-MDM2 Interaction. J. Am. Chem. Soc. (2005), 127, 10130-10131.（IF = 8.09）
34. Ke Ding, Jianyong Chen, Min Ji, Xihan Wu, Judith Varady, Beth Levant and Shaomeng Wang. Design, synthesis and evaluation of enantiomerically pure substituted hexahydropyrazinolines as potent and highly selective Dopamine 3 receptor ligands. J. Med. Chem. (2005), 48, 3171-3181. (IF = 4.90)
35. Ke Ding, Guoping Wang, Jeffrey R. Deschamps and Shaomeng Wang. Spirooxindoles via asymmetric 1,3-dipolar cycloaddition. Tetrahedron Letters. (2005), 46, 5949-5951. (IF = 2.53)
36. Ke Ding and Shaomeng Wang. An Efficient synthesis of isoflavone analogues via a Suzuki coupling reaction. Tetrahedron Letters. (2005), 46, 3707-3709. (IF = 2.53)
37. Min Ji, Jianyong Chen, Ke Ding, Xihan Wu, Judith Varady, Beth Levant and Shaomeng Wang. Design, synthesis and structure–activity relationship studies of hexahydropyrazinoquinolines as a novel class of potent and selective dopamine receptor 3 (D3) ligands. Bioorg. & Med. Chem. Letts. (2005), 15 (6), 1701-1705. (IF = 2.53)
38. Ke Ding, Judy Flippen-Anderson, Jeffrey R. Deschamps and Shaomeng Wang. An efficient synthesis of optically pure (S)-2-functionalized 1,2,3,4-tetrahydroquinoline. Tetrahedron Letters (2004), 45(5), 1027-1029. (IF = 2.54) 39. Dawei Ma, Ke Ding, Hongqi Tian, Baomin Wang and Dongliang Chen. Asymmetric synthesis of (S)-1-aminoindan-1, 5-dicarboxylic acid and related analogues via intramolecular acylation of enantiopure a,a-disubstituted amino acids. Tetrahedron: Asymmetry (2002), 13(9), 961-969. (IF = 2.80)
40. Ke Ding, Xinrong Zhang, Dawei Ma and Baomin Wang. Synthesis and biological activity of 1-aminoindan-1,3-dicarboxylic acid, a benzo analogue of (1S, 3 R) ACPD. Chinese Journal of Chemistry. (2001), 19(12), 1232-1238. (IF = 0.95)
41. Ke Ding and Dawei Ma. Asymmetri synthesis of a,a-disubstituted amino acids by diastereoselective functionalization of enantiopure phenyloxazinone, derivatives of asymmetric Strecker reaction products of aldehydes. Tetradetron. (2001), 57(30), 6361-6366. (IF =2.90)
42. Dawei Ma and Ke Ding. Synthesis of enantiopure a,a-disubstituted amino acids from asymmetric Strecker reaction products of aldehydes. Organic Letters. (2000), 2 (16), 2515-2517. (IF = 5.13)
43. Deping Wang，Zhang Zhang，Xiaoyun Lu, Yubing Feng, Kun Luo, Jirong Gan, Yingxue Liu, Junting Lu, Xiang Li, Fengxiang Zhang, Zhengchao Tu, Qian Cai, Xiaomei Ren, ﹡Ke Ding.Hybrid Compounds as New Bcl/Abl Inhibitors Bioorg.Med.Chem.Lett(2011)DOI:10.1016/j.bmcl.2010.02.29
44. ﹡Qian Cai, Fengtao Zhou, Tianfeng Xu, Liangbin Fu, ﹡Ke Ding Copper-Catalyzed Tandem Reactions of 1-(2-Iodoary)-2-yn-1-ones with Isocyaanides for the Synthesis of 4-Oxo-indeno[1,2-b]pyrroles Organic Letters(2011),13,340-343
45. Xiujie Liu, Xiaoli Huang, Dongye Wang, Yanyan Diao, Honglin Li, Xiaoyan Hui, Yi Wang, Aimin Xu, Dnonghai Wu, ﹡Ke Ding. New Aromatic Substituted Pyrazoles as Selective Inhibitors of Human Adipocyte Fatty Acid-Binding Protein Bioorg.Med.Chem.Lett(2011),21,p000

指导学生请况已指导学生

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