主要研究小分子化合物化學庫、天然產(chǎn)物、多肽/糖肽、以及“協(xié)同治療”分子的合成方法；同時，實驗室也研究高通量篩選方法用于了解分子間的相互作用、編碼及解碼可干擾生物活性作用的小分子化合物。實驗室的目標是發(fā)現(xiàn)藥物先導化合物并優(yōu)化為藥物候選物用于治療癌癥及感染性疾病。
劉剛教授是我國最早從事組合化學和化學生物學研究者之一，成功搭建了由高通量合成技術(shù)、高通量現(xiàn)代分析技術(shù)、藥物化學、有機化學、高分子化學（樹脂）、計算化學、自動化技術(shù)、生物篩選技術(shù)、數(shù)據(jù)管理系統(tǒng)、以及樣品保存和質(zhì)控分析方法等多學科和技術(shù)支撐的系統(tǒng)組合化學技術(shù)平臺，被專家鑒定為“整體處于國際先進水平”。多年來在小分子雜環(huán)化合物化學庫的設(shè)計與組合合成、多肽化學以及多肽模擬物化學、有機化學、藥物化學、以及免疫治療、抗腫瘤和抗感染性疾病的藥物研究方面都積累了豐富的研究及應用經(jīng)驗，取得了一些重要的結(jié)果。
實驗室發(fā)現(xiàn)的紫杉醇或者多西紫杉醇與胞壁酰二肽衍生物物的共綴物“康莫他賽”及“信立他賽”，設(shè)計為通過拮抗NOD1 or NOD2信號通路的活化，負調(diào)節(jié)腫瘤化療導致的炎性微環(huán)境，逆轉(zhuǎn)化療抵抗，進而抑制腫瘤的轉(zhuǎn)移性生長。該項目的研究歷時20余年，目前正在開展臨床試驗。
1. 模式識別受體NOD1/2拮抗劑逆轉(zhuǎn)化療抵抗抑制腫瘤轉(zhuǎn)移性生長（J Extracell Vesicles, 2022; 11: e12264；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化學庫的合成及其抗HIV-1、抗結(jié)核桿菌活性及靶點和結(jié)核單細胞熒光診斷試劑研究(Chem Commun (Camb). 2021, 57, 13174-13177；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. 天然產(chǎn)物全合成及小分子雜環(huán)合成及藥物化學(J. Med. Chem., 2022, 65, 21, 14891-915.; Angew. Chem. Int. Ed., 2016, 55(24): 6992-6; Org Lett 2015, 17(16): 4110-3.)。
代表性文章
1. Xiduan Wei, Jingjia Ye, Yamen Pei, Chunting Wang, Hongzhen Yang, Jingyuan Tian, Guangxu Si, Yao Ma*, Kun Wang*, Gang Liu*, Extracellular vesicles from colorectal cancer cells promote metastasis via the NOD1 signaling pathway, J Extracell Vesicles, 2022, 11: e12264.
2. Wenjun YU, Yao Ma, Xilei Xie, Shiping Fang, Yi Dong*, Gang LIU*, Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Protein Synthesis Inhibitors with Highly Potent Anticancer Activity, J. Med. Chem. 2022, 65(21), 14891-14915.
3. Xueyuan Li, Pengfei Geng, Xiaoqiao Hong, Zhaogang Sun, Gang Liu*, Detecting Mycobacterium Tuberculosis using a nitrofuranyl calanolide–trehalose probe based on nitroreductase Rv2466c, Chem Commun (Camb). 2021, 57, 13174-13177.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Yi Dong, Gang Liu*，Rh-Catalyzed Sulfonic Acid Group Directed C-H Olefination of Arenes, Chem. Comm. 2013, 49, 8066-8068.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
