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Ding's Laboratory


Ke Ding, Ph. D.
Principal Investigator
Director of Chemical Biology Institute


Dr. Ding obtained his Ph.D. in Fudan University and Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences in 2001 after graduating from the China Pharmaceutical University. He received his post-doctoral training in University of Michigan during 2001-2004, and then worked as a Research Investigator. In 2006, Dr. Ding joined Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences as a Senior Principal Investigator, Doctoral Supervisor and Deputy Director of Chemical Biology Institute. He was an enlisted scientist for “Hundred-Talent Program of CAS” in 2007 and an outstanding expert of the city of Guangzhou in 2008. Dr. Ding obtained the “Ding Ying Science and Technology award of Guangdong Province” in 2009. In 2010, He became one of the two Advisory Editorial Board Members of ACS Medicinal Chemistry Letter in China. Dr. Ding is also the Vice Chairmen of the Medicinal Chemistry Committee of Guangdong Pharmaceutical Association, Director of Guangdong Association of Young Scientists (GDAYS) and member of Youth Federation of Chinese Academy Sciences and Guangzhou Youth Federation.

Dr. Ding’s researches mainly focuses on the discovery of small molecules targeting key functional proteins, which may be potentially developed as new drugs to treat cancer or metabolic diseases. In the U.S., he participated in the study of the broad-spectrum inhibitors of Bcl-2 family protein, of which anticancer drug (AT-101) has entered Phase III clinical development in the United States. He was also responsible for the design and synthesis of the Spirooxindole type p53-MDM2 inhibitors and isoflavones Bcl-2 family protein inhibitors, which had been licensed to Sanofi-aventis and Ascenta Therapeutic Company, respectively. After returning to the Chinese Academy of Sciences Guangzhou Institutes of Biomedicine and Health, he led a research team to successfully design and synthesis the arguably first ERR first agonist as new potential drug to treat metabolic disorders (which has cooperated a new company in Hongkong); the new Bcr-Abl inhibitors to overcome the clinical resistance against Gleevec. In addition, closely collaborating with biologists, he has successfully designed and synthesized subtype selective FABP4 inhibitors, Aggrecanases ADAMTS inhibitors, and small molecule STAT3 inhibitors, etc.

Dr. Ding has published more than 50 papers in JACS, JMC, PNAS, etc. and been co-inventor for more than 20 patents, part of which had successfully been licensed to some international pharmaceutical companies.

Personnel: 


Research:


Publications:
2011
1. 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.
2. Xiaoyun Lu, Qian Cai and Ke Ding. Recent Developments in the Third Generation Inhibitors of Bcr-Abl for Overriding T315I mutation, Current Medicinal Chemistry, 2011, 18(14): 2146-57.
3. Fengtao Zhou, Jianguang Liu, Ke Ding, Jinsong Liu, and Qian Cai. Copper-Catalyzed Tandem Reaction of Isocyanides with N-(2-Haloaryl) propiolamides for the Synthesis of Pyrrolo[3,2-c]quinolin-4-ones . J. Org. Chem., 2011, 76 (13), 5346-5353.
4. 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, 2949-2952.
5. Lijie Peng, Lei Duan, Xiaofeng Liu, Mengjie Shen, Yingjun Li, Jiajie Yan, Honglin Li, Ke Ding. Structure–activity study on a series of α-glutamic acid scaffold based compounds as new ADAMTS inhibitors .Bioorganic & Medicinal Chemistry Letters, 2011, 21, 4457- 4461.
6. Deping Wang, Zhang Zhang, Xiaoyun Lu, Yubing Feng, Kun Luo, JirongGan, Yingxue Liu, Junting Lu, Xiang Li, Fengxiang Zhang, Zhengchao Tu, Qian Cai, Xiaomei Ren and Ke Ding. Hybrid Compounds as New Bcr-Abl Inhibitors. Bioorg Med Chem Lett. 2011, 21(7): 1965-1968.
7. 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, 2011, 21, 205-212.
2010
1. Xiaomei Ren, Qiang He; Lei Duan, Zhang Zhang, Yi Zhou, Donghai Wu, Jingxuan Pan, Duanqing Pei, Ke Ding*. Identification of a New Small-Molecule Inhibitor of STAT3 Signaling Pathway by Using a “Repositioning” Strategy. ACS Med. Chem. Lett. 2010, 2010, 1 (9), 454–459.
2. 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.
3. Qian Cai, Jiajia Wei, Liangbin Fu, Duanqing Pei, Ke Ding*. Synthesis of Aza-Fused Polycyclic Quinolines through Copper-Catalyzed Cascade Reactions. Org. Lett. 2010, 12(7): 1500-1503.
4. 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.
5. Zhengqiu Lia, Liangbin Fub, Jiajia Wei, Chengyong Ha, Duanqing Pei, Qian Cai*, Ke Ding*. A Room-Temperature, Copper-Catalyzed Cascade Process for Diethyl 2-Aryl-3,4-dihydro-4-oxo-1,1(2H)-naphthalenedicarboxylate. Synthesis, 2010, 9, 3289-3294.
6. 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.
7. 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.
8. 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, 9,640-650.
2009
1. Deping Wang, Ke Ding*. 2-Pyridinyl beta-Ketones as New Ligands for Room-Temperature CuI-Catalysed C-N Coupling Reactions. Chem. Comm., 2009, 1891-1893.
2. Qian Cai, Zhengqiu Li, Jiajia Wei, Chengyong Ha, Duanqing Pei, Ke Ding*. Assembly of indole-2-carboxylic acid esters through a ligand-free copper-catalysed cascade process. Chem. Commun., 2009, 48, 7581-7583.
3. Deping Wang, Qian Cai, Ke Ding*. An Efficient Cu-Catalyzed Amination of Aryl Halides by Aqueous Ammonia. Adv. Synth. Cata., 2009, 351, 1722-1726.
4. Jing Zhou, Lei Duan, Huaming Chen, Xiaomei Ren, Zhang Zhang, Fengtao Zhou, Jinsong Liu , Duanqing Pei, Ke Ding*. Atovaquone Derivatives as Potent Cytotoxic and Apoptosis Inducing Agents. Bioorg. Med. Chem. Lett., 2009, 19, 5091-5094.
5. 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.
6. 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.
7. 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.
2008
1. 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, 2008, 7, 845-852.
2. Wang, Deping; Kuang, Liping; Li, Zhengwei; Ding, Ke*. L-proline Promotes Rosenmund-Von Braun Reaction. SynLett, 2008, 69-72.
3. 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.
4. 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.
5. Wang, G, Li, Z, Ha, C, Ding, K*. Direct oxidation of N-benzylamides to aldehydes or ketones by N-bromosuccinimide. Synthetic Communications, 2008, 38, 1629-1637.
6. 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 American 2008, 105, 3933-3938.
7. 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, 1533-1542.
8. Jiang, Sheng; Li, Zheng; Ding, Ke; Roller, Peter P. Recent progress of synthetic studies to peptide and peptidomimetic cyclization Current Organic Chemistry 2008, 12, 1502-1542.
9. 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.
2007
1. Kuang, Liping; Zhou, Jing; Chen, Sheng; Ding, Ke*. Room-Temperature Debenzylation of N-Benzylcarboxamides by N-Bromosuccinimide. Synthesis ,2007, 3129 - 3134.
2. 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, 3163-3166.
3. 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, 471-81.
2006
1. 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.
2. 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.
3. 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.
2005
1. 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.
2. 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.
3. Ke Ding, Guoping Wang, Jeffrey R. Deschamps and Shaomeng Wang. Spirooxindoles via asymmetric 1,3-dipolar cycloaddition. Tetrahedron Letters. 2005, 46, 5949-5951.
4. Ke Ding and Shaomeng Wang. An Efficient synthesis of isoflavone analogues via a Suzuki coupling reaction. Tetrahedron Letters. 2005, 46, 3707-3709.
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