师资队伍 | 刘刚, PhD

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,并于同年及2005年被分别授予“协和学者”特聘教授及教育部“长江学者”特聘教授。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,现任或曾任Associate Editor of “Molecular Diversity”,曾或现任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,现任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、以及中国药学会药学教育专业委员会委员,北京药学会药物化学专业委员会委员。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120余篇研究性论文,申请国际国内专利二十余项。


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。

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. 2018, 61, 1519-1540; 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, 4, 771-787.; 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.)。

荣誉和奖项

1、第十五届中国药学会科学技术奖,一等奖,2019年
2、12th Chinese International Peptide Symposium,Cathay award of 2012
3、清华大学“百人计划”特聘教授,2011年
4、药明康德生命化学研究奖三等奖,2007年
5、北京市科学技术进步三等奖,2006年

代表性论文

1. Chunting Wang, Yameng Pei, Lei Wang, Ye Xiang, Yao Ma*, Gang Liu*, Constrain the Conformation: Discovery of (1H-pyrazolo[3,4-c]pyridin-5-yl)sulfonamide Analogues as Hepatitis B Virus Capsid Assembly Modulator, J. Med. Chem., 2020, 63, 6066-6089.
2. Yao Ma, Dawei Yin, Hai Qian*, Gang Liu*, Discovery of potent inhibitors against P-glycoprotein-mediated multidrug resistance aided by late-stage functionalization of 2-(4-(pyridin-2-yl)phenoxy)pyridine analogue, J. Med. Chem. 2020, 63, 5458-5476.
3. Ran Mu, Chengcheng Kong, Wenjun Yu, Hongyao Wang, Jie Wu, Xueyuan Li, Selin Somersan-Karakaya, Haitao Li, Zhaogang Sun*, Gang LIU*, Nitrooxidoreductase Rv2466c-Dependent Fluorescent Probe for Mycobacterium tuberculosis Diagnosis and Drug Susceptibility Testing, ACS Infect. Dis. 2019, 5(6), 949-961.
4. 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*, and Gang 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.
5. 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.
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. 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.
9. 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.
10. 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.
11. Yi Dong, Gang Liu*,Rh-Catalyzed Sulfonic Acid Group Directed C-H Olefination of Arenes, Chem. Comm. 2013, 49, 8066-8068.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.