刘刚 长聘教授，博士生导师


刘刚教授1994年毕业于北京医科大学药学院并获博士学位。1994年至1997年间前后于军事医学科学院毒物药物研究所及The Scripps Research Institute从事博士后研究工作。后作为高级研究助理在美国加州大学戴维斯分校工作。2000年回到中国医学科学院药物研究所建立了自己的实验室。2011年始任清华大学百人教授，在清华大学医学院负责筹建药学系，并担任首任药学系主任。曾兼任中华人民共和国农业部第五届兽药评审专家，现任Associate Editor of “Molecular Diversity”，Journal of Medicinal Chemistry、《中国药物化学杂志》、《中国药学》（英文版）、《药学学报》、《中国病毒病杂志》等期刊编委，中国药学会药物化学专业委员会委员，教育部高等学校药学类专业教学指导委员会委员、以及中国药学会第一届药学教育专业委员会委员。曾主持美国国家健康研究所（NIH）R01抗SARS-CoV项目，参与Bill & Melinda Gates Foundation的抗结核项目；主持或参与过国家科技部（“863”，“973”）项目、国家重大新药创制项目、国家自然科学基金各类项目，人事部、教育部、卫生部以及企业等多项基金项目。出版《新药研究中的组合化学》一部、英文图书两章、中文图书一章。发表110余篇研究性论文。多次受邀在国际学术会议上进行大会口头报告。申请国际国内专利二十余项。主持开发的抗肿瘤药物候选物（康莫他赛及信立他赛）已获SFDA批准临床研究。

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研究方向实验室主要研究小分子化合物化学库、天然产物、多肽/糖肽、以及“协同治疗”分子的合成方法；同时，实验室也研究高通量筛选方法用于了解分子间的相互作用、编码及解码可干扰生物活性作用的小分子化合物。实验室的目标是发现药物先导化合物并优化为药物候选物用于治疗癌症及感染性疾病。

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研究成果与贡献刘刚教授是我国最早从事组合化学和化学生物学研究者之一，成功搭建了由高通量合成技术、高通量现代分析技术、药物化学、有机化学、高分子化学（树脂）、计算化学、自动化技术、生物筛选技术、数据管理系统、以及样品保存和质控分析方法等多学科和技术支撑的系统组合化学技术平台，被专家鉴定为“整体处于国际先进水平”。多年来在小分子杂环化合物化学库的设计与组合合成、多肽化学以及多肽模拟物化学、有机化学、药物化学、以及免疫治疗、抗肿瘤和抗感染性疾病的药物研究方面都积累了丰富的研究经验，取得了一些重要的研究结果。
实验室发现的紫杉醇或者多西紫杉醇与胞壁酰二肽衍生物物的共缀物“康莫他赛”及“信立他赛”，设计为通过拮抗NOD1 or NOD2信号的活化，负调节肿瘤化疗导致的炎性微环境，改善化疗抵抗，抑制肿瘤的转移性生长，已获得CFDA批准进入临床研究阶段。
1. 模式识别受体NOD1/2拮抗剂逆转化疗抵抗抑制肿瘤转移性生长（J. Med. Chem. Jan. 2018, online; J. Med. Chem. 2017, 60 (12), 5162–5192.; J. Med. Chem. 2017, 60, 1219-1224; J. Med. Chem. 2011, 54(8): 2767-77; Glycoconj J 2008, 25: 415–425.）。
2.天然(+)-Calanolide A化学库的合成及其抗HIV-1、抗非复制性结核杆菌活性及靶点研究(ACS Infect. Dis. 2018, Jan. 2018, accepted; J. Med. Chem., 2014, 57, 3755-3772.; Antimicrob. Agents Chemother. 2012, 56(1): 341-351.; J. Med. Chem. 2010, 53, 1397–1401.; J. Med. Chem. 2008, 51, 1432–1446. )。

3. SARS冠状病毒抗原表位的研究：抗原依赖的抗体对非人类灵长类动物感染的增强、抑制或中和作用(ACS Infect. Dis. 2016, 2, 361−376；J. Combi. Chem. 2005, 7, 648-656.)。
4. 天然产物全合成及金属催化的交叉偶联去芳香化/环化反应构建 [3.2.1]桥环骨架类化合物(Angew. Chem. Int. Ed., 2016, 55(24): 6992-6; Org Lett 2015, 17(16): 4110-3.)。

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荣誉和奖项1. 北京市科学技术进步三等奖，2006年
2. 药明康德生命化学研究奖三等奖，2007年
3. 清华大学“”，2011年
4. 12th Chinese International Peptide Symposium，Cathay award of 2012
5. 中国药学会药物化学专业委员会委员
6. 教育部高等学校药学类专业教学指导委员会委员
7. 中国药学会第一届药学教育专业委员会委员

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代表性论文1. Xiaoming Wen,Purong Zheng,Yao Ma,Yingye Ou,Weixin Huang,Shuo Li,Shoujia Liu,Xuan Zhang,Ziyu Wang,Qianli Zhang,Wenming Cheng,Ruwen Lin,Hongzu Li,Youyou Cai,Chunyun Hu,Ningbin Wu,Long Wan,Tingting Pan,Jinlong Yao,Xuelu Bei,Wei-Bin Wu,Jian Jin,Jie Yan*, andGang Liu*, Salutaxel, a conjugate of docetaxel and a muramyl dipeptide (MDP) analogue, acts as multi-functional prodrug that inhibits tumor cell growth and metastasis, J. Med. Chem. 2018, 61, 1519-1540.
2. Ana Negri, Prisca Javidnia, Ran Mu, Xiaojie Zhang, Jeremie Vendome, Ben Gold, Julia Roberts, Dipti Barman, Thomas Ioerger, James Sacchettini, Xiuju Jiang, Kristin Burns-Huang, Thulasi Warrier, Yan Lin, David Warren, Thijs Beuming, Hongyao Wang, Jie Wu, Haitao Li, Kyu Rhee, Carl F. Nathan, Gang Liu*, Selin Somersan-Karakaya^*, Identification of a mycothiol-dependent nitro-oxidoreductase from Mycobacterium tuberculosis, ACS Infect. Dis. Jan. 2018, online.
3. Suhua Wang,Jingshu Yang,Xueyuan Li,Zijie Liu,Youzhen Wu,Guangxu Si,Yiran Tao,Nan Zhao,Xiao Hu, Yao Ma*, Gang Liu*, Discovery of 1,4-Benzodiazepine-2,5-dione (BZD) Derivatives as Dual Nucleotide Binding Oligomerization Domain Containing 1 /2 (NOD1/NOD2) Antagonists Sensitizing Paclitaxel (PTX) to Suppress Lewis Lung Carcinoma (LLC) Growth In Vivo, J. Med. Chem. 2017, 60 (12), 5162–5192.
4. Bo Liu, Xue Liu, Jingren Zhang*, Gang Liu*, A Natural Lipotrisaccharide and Its Derivatives Selectively Lyse Streptococcus pneumoniae via Interaction with Cell Membrane, ACS Infect. Dis. 2017, 3, 438-453.
5. Yi Dong, Gang Liu*, Auxiliary-Assisted Palladium-Catalyzed Direct C(sp3)−H Sulfonamidation To Afford 1,2-Amino Alcohol Derivatives. J. Org. Chem. 2017, 82, 3864-3872.
6. Yi Dong, Suhua Wang, Chunting Wang, Zihua Li, Yao Ma*, Gang Liu*, Antagonizing NOD2 Signaling with Conjugates of Paclitaxel and Muramyl Dipeptide Derivatives Sensitizes Paclitaxel Therapy and Significantly Prevents Tumor Metastasis, J. Med. Chem. 2017, 60, 1219-1224.
7. Yameng Pei, Chunting Wang, S. Frank Yan*, Gang Liu*，Past, Current, and Future Developments of Therapeutic Agents for Treatment of Chronic Hepatitis B Virus Infection，J. Med. Chem. 2017, 60, 6461-6479. Invited perspective.
8. Maojin Li, Rouli Zhou*, Yi Shan, Li Li, Lin Wang, Gang Liu*, Targeting a novel cancer-driving protein (LAPTM4B-35) by a small molecule (ETS) to inhibit cancer growth and metastasis, Oncotarget. 2016, 7(36), 58531-58542.
9. Qidi Wang, Lianfeng Zhang, Kazuhiko Kuwahara, Li Li, Zijie Liu, Taisheng Li, Hua Zhu, Jiangning Liu, Yanfeng Xu, Jing Xie, Hiroshi Morioka, Nobuo　Sakaguchi*, Chuan Qin*, Gang LIU*, Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-Human Primates, ACS Infect. Dis. 2016, 2, 361−376.
10. Chong Tian, Xiaoqiang Lei, Yuanhao Wang, Zhen Dong, Gang Liu* and Yefeng Tang*, Total Syntheses of Periconiasins?A-E, Angew. Chem. Int. Ed., 2016, 55(24): 6992-6.
11. Nan Zhao, Mingna Sun, Kristin E. Burns-Huang, Xiuju Jiang, Yan Ling, Crystal M. Darby, Sabine Erht, Gang Liu* and Carl F. Nathan*, Identification of Rv3852 as an Agrimophol-Binding Protein in Mycobacterium tuberculosis, PLoS One 2015, 10(5): e**.
12. Xueyuan Li, Yi Dong, Fengyu QU*, Gang Liu*, Synthesis of benzofused five-ring sultams via Rh-catalyzed CH olefination directed by an N-Ac substituted sulfonamide group, J. Org. Chem. 2015, 80, 790−798.
13. Yi Dong, Nana Du, Xueyuan Li, Litao Zheng, Gang Liu*, Tandem Chloropalladation/Cyclization and Dearomative Cyclization toward Functionalized Tricyclic Bridged [3.2. 1] Skeleton Compounds, Org. Lett. 2015, 17(16):4110-3.
14. Zijie Liu, Youzhen Wu, Gang Liu*, Efficient and convenient total synthesis of mycothiol on a large scale, J. Chin. Pharm. Sci. 2015, 24(6), 347-355.
15. Purong Zheng, Selin Somersan Karakaya, Shichao Lu, Julia Roberts, Maneesh Pingle, Thulasi Warrier, David Little, Xiaoyong Guo, Steven Brickner, Carl F. Nathan*, Ben Gold*, Gang Liu* Synthetic Calanolides with Bactericidal Activity Against Replicating and Non-replicating Mycobacterium tuberculosiss, J. Med. Chem. 2014, 57(9), 3755–3772.
16. Hong-Shuang Li, Gang Liu*, Copper/Silver-Mediated Cascade Reactions for the Construction of 2-Sulfonylbenzo[b]furans from trans-2-Hydroxycinnamic Acids and Sodium Sulfinates, J. Org. Chem. 2014, 79, 509−516.
17. Bo Liu, Fa Zhang, Yan Zhang, Gang Liu*, A new approach for the synthesis of O-glycopeptides through a combination of solid-phase glycosylation and fluorous tagging (SHGPFT), Org. Biomol. Chem., 2014, 12, 1892–1896.
18. Xilei Xie, Yu Yan, Ning Zhu, Gang Liu*, Benzothiazoles exhibit broad-spectrum antitumor activity: their potency, structure-activity and structure-metabolism relationships, Eur. J. Med. Chem. 2014, 76, 67-78.
19. Yaling Gong, Selin Somersan Karakaya, Purong Zheng, Ben Gold, David Little, Julia Roberts, Thulasi Warrier, Xiuju Jiang, Maneesh Pingle, Carl F. Nathan*, Gang Liu*, Benzimidazole-Based Compounds Kill Mycobacterium tuberculosis, Eur. J. Med. Chem. 2014, 75, 336-353.
20. Yingwei Hou, Shichao Lu and Gang Liu*, Iodine (III)-mediated [3+2] cyclization for one-pot synthesis of benzo[d]isoxazole-4,7-diol, benzodiisoxazole-4,8-diol, isoxazole[5,4-a]phenazine and indazole-4,7-diol in aqueous medium, J. Org. Chem. 2013, 78, 8386−8395.
21. Yi Dong, Gang Liu*，Rh-Catalyzed Sulfonic Acid Group Directed C-H Olefination of Arenes, Chem. Comm. 2013, 49, 8066-8068.
22. Mingna Sun, Jinfeng Hu, Xiuyun Song, Donghui Wu, Linglei Kong, Yupeng Sun, Dongmei Wang, Yan Wang^*, Naihong Chen* and Gang Liu*, Coumarin Derivatives Protect Against Ischemic Brain Injury in Rats, Eur. J. Med. Chem. 2013, 67, 39-53.
23. Shichao Lu, Purong Zheng, Gang Liu*, Iodine(III)-Mediated Tandem Oxidative Cyclization for Construction of 2-Nitrobenzo[b]furans, J. Org. Chem. 2012, 77, 7711-7717.
24. Xiaofan Lu, Li Liu, Xu Zhang, Terrence Lau, Stephen Kwok-Wing Tsui, Yuanxi Kang, Purong Zheng, Gang Liu^* and Zhiwei Chen^*, F18, a novel small molecule NNRTI, inhibits HIV-1 replication using distinct binding motifs, Antimicrob. Agents Chemother. 2012, 56(1): 341-351.
25. Rui Liu, Zhuhui Huang, Michael G. Murray, Xiaoyong Guo, Gang Liu*, Quinoxalin-2(1H)-One Derivatives As Inhibitors Against Hepatitis C Virus, J. Med. Chem. 2011, 54, 5747–5768.
26. Yao Ma, Nan Zhao, Gang Liu*, Conjugate (MTC-220) of Muramyl Dipeptide Analogue and Paclitaxel Prevents Both Tumor Growth and Metastasis in Mice, J. Med. Chem.,2011,54(8), 2767–2777.
27. Gang Li, Dongmei Wang, Mingna Sun, Guangyan Li, Jinfeng Hu, Yun Zhang, Yuhe Yuan, Haijie Ji, Naihong Chen*, Gang Liu*. Discovery and Optimization of Novel 3-Piperazinyl Coumarin Antagonist of Chemokine – like factor 1 with oral Anti-asthma activity in mice. J. Med. Chem. 2010, 53 (4), 1741–1754.
28. Hai Xue, Xiaofan Lu, Purong Zheng, Li LIU, Chunyan Han, Jinping HU, Zijie Liu, Tao MA, Yan LI, Lin WANG , Zhiwei CHEN*, Gang LIU*, Highly suppressing wide type HIV-1 and Y181C mutation by 10-Chloromethyl-11-Demethyl-12-oxo calanolide A with druggable profile. J. Med. Chem. 2010, 53, 1397–1401.
29. Leilei Zhang, Yu Yan, Zijie Liu, Abliz Zeper, Gang Liu*, Identification of Peptide Substrate and Small Molecule Inhibitors of Testis-specific Serine/Threonine Kinase1 (TSSK1) By the Developed Assays, J. Med. Chem. 2009, 52, 4419-4428.
30. Fa Zhang, Wei Zhang, Yan Zhang, Dennis P. Curran, and Gang Liu*, Synthesis and Applications of Light-Fluorous Glycosyl Donor, J. Org. Chem. 2009, 74 (6), 2594-2597.
31. Tao MA, Li LIU, Hai XUE, Li LI, Chunyan HAN, Lin WANG, Zhiwei CHEN, Gang LIU*, The Chemical Library and Structure-Activity Relationship of Calanolide-A Analogues against HIV-1, J. Med. Chem. 2008, 51, 1432-1446.
32. Xuqin Li, Junli Yu, Song Xu, Nan Wang, Hongzhen Yang, Zheng Yan, Guifang Cheng, Gang Liu*, Chemical Conjugation of Muramyl Dipeptide and Paclitaxel to Explore the Combination of Immunotherapy and Chemotherapy for Cancer, Glycoconj. J. 2008, 25: 415-425.
33. Tao MA, Qi GAO, Zhiwei Chen, Lin WANG, Gang LIU*, Chemical Resolutions of (±)-Calanolide A, (±)-Cordatolide A and Their 11-Demethyl Derivatives, Bioorg. Med. Chem. Letts. 2008，18, 1079–1083.
34. Tian-Ming Yang, Gang Liu*, Solution-Phase Parallel Synthesis of 3-Substituted Indolin-2-ones, J. Comb. Chem. 2007, 9, 86-95.
35. Hongbo Hu, Li Li , Richard Y. Kao, Binbin Kou, Zhanguo Wang, Liang Zhang, Huiyuan Zhang, Zhiyong Hao, Wayne H. Tsui, Anping Ni, Lianxian Cui, Baoxing Fan, Feng Guo, Shuan Rao, Chengyu Jiang, Qian Li, Manji Sun, Wei He*, Gang Liu*, Screening and Identification of Linear B-cell Epitopes and Entry Blocking Peptide of Severe Acute Respiratory Syndrome (SARS) Associated Coronavirus Using Synthetic Overlapping Peptide Library, J. Comb. Chem. 2005, 7, 648-656.
36. Hong-Zhen Yang, Song Xu, Xue-Yan Liao, Suo-De Zhang, Zheng-Lun Liang, Bai-He Liu, Jin-Ye Bai, Chao Jiang, Jian Ding, Gui-Fang Cheng*, Gang Liu*, A novel immunostimulator, N²-[a-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N⁶-trans-(m-nitrocinnamoyl)-L-lysine (MDP-C), and its adjuvancy on the hepatitis B surface antigen, J. Med. Chem. 2005, 48, 5112-5122.