尚鲁庆教授

学科方向：药物化学与化学生物学

通讯地址：南开大学药学院天津市海河教育园区同砚路38号，300350

电子邮件：shanglq@nankai.edu.cn

南开大学药学院教授，博导，南开大学药学院副院长，药学实验教学中心主任，天津市创新人才推进计划青年科技优秀人才。2004年7月毕业于山东大学药学院；2009年7月毕业于山东大学药学院，获药物化学博士学位。期间赴日本和歌山县立医科大学药理学专业交流学习一年。2009年7月加入南开大学药学院。2017年9月-2018年9月赴美国佐治亚州立大学作访问学者。主持多项国家自然科学基金重点及面上课题、科技部重点研发计划课题和天津市科委重点项目。近年来在ACS Catalysis，ACS Sens.，J. Med. Chem., Org. Lett. Antimicrob. Agents. Chemother.等国际期刊发表SCI论文30余篇，获授权专利五项。

研究方向

以肠病毒属、冠状病毒属、黄病毒属等病毒关键蛋白为研究对象，围绕致病性病毒进行系统性的抗病毒药物研究工作。将药物分子设计技术、结构生物学及比较生物学有效结合，发展原创性的靶点蛋白抑制剂，阐述蛋白分子与小分子探针的结合模式，揭示蛋白分子的生物特异性，开展初步的药效学评价和药物动力学研究，发展具有开发前景的临床前候选药物。2020年本课题组揭示了冠状病毒主蛋白酶的催化机制，讨论了冠状病毒MERS-CoV与SARS-CoV主蛋白酶在催化过程中的区别，进而优化了主蛋白酶抑制剂的生物活性，为未来应对冠状病毒的变异奠定了研究基础，该成果的论文发表在美国化学会期刊《ACS Catalysis》上。

代表论文

1.Comprehensive Insights into the Catalytic Mechanism of Middle East Respiratory Syndrome 3C-Like Protease and Severe Acute Respiratory Syndrome 3C-Like Protease. Hao Wang, Shuai He, Weilong Deng, Ying Zhang, Guobang Li, Jixue Sun, Wei Zhao, Yu Guo, Zheng Yin, Dongmei Li*, and Luqing Shang*.ACS Catalysis 2020, 10, 10, 5871-5890.

2.Establishment of a Customizable Fluorescent Probe Platform for the Organelle-Targeted Bioactive Species Detection. Dan Qiao, Landie Li, Tangliang Shen, Jiejie Yang, Hao Chang, Xiao Liang, Lu Zhang, Qianqian Wang, Ning Liu, Wei Zhao, and Luqing Shang*.ACS Sens. 2020, 5, 7, 2247-2254.

3. Application of dually activated Michael acceptor to the rational design of reversible covalent inhibitor for Enterovirus 71 3C protease. Yuying Ma, Linfeng Li, Shuai He, Chengyou Shang, Yang Sun, Ning Liu, Thomas Meek, Ya Xin Wang*,Luqing Shang*. J. Med. Chem., 2019, 62, 6146-6162.

4. An ICT-based mitochondria-targeted fluorescent probe for hydrogen peroxide with a large turn-on fluorescence signal. Xiao Liang, Lu Zhang, Xiaoyi Xu, Dan Qiao, Tangliang Shen, Zheng Yin,Luqing Shang*. Chemistry Select, 2019, 4(4), 1330-1336.

5. 4‐Iminooxazolidin-2-one as a bioisostere of the cyanohydrin moiety: inhibitors of enterovirus 71 3C protease. Yuying Ma, Chengyou Shang, Peng Yang, Linfeng Li, Yangyang Zhai, Zheng Yin, Binghe Wang*,Luqing Shang*. J. Med. Chem., 2018, 61, 22, 10333-10339.

6. A highly selective and sensitive fluorescent probe for simultaneously distinguishing and sequentially detecting H2S and various thiol species in solution and in live cells. Dan Qiao, Tangliang Shen, Mengyuan Zhu, Xiao Liang, Lu Zhang, Zheng Yin, Binghe Wang*,Luqing Shang*. Chem. Commun., 2018, 54, 13252-13255.

7. 3D-quantitative structure-activity relationship study for the design of novel。enterovirus A71 3C protease inhibitors. Quandeng Nie, Xiaoyi Xu, Qi Zhang, Yuying Ma, Zheng Yin,Luqing Shang*. Chem Biol Drug Des. 2018, 92(4), 1750-1762.

8.Target-guided screening of fragments (TGSOF) in the discovery of inhibitors against EV-A71 3C protease. Shengjun Fu, Quandeng Nie, Yuying Ma, Ping Song, Xuejiao Ren, Cheng Luo,Luqing Shang*, Zheng Yin*. Chem. Commun.,2018, 54, 2890-2893.

9. Dual mechanism ICT-FRET-based fluorescent probe for the selective detection of hydrogen peroxide. Xiao Liang, Xiaoyi Xu, Dan Qiao, Zheng Yin, Luqing Shang*. Chem-Asian J. 2017, 2017,12, 3187-3194.

10. Structure of the Enterovirus 71 3C protease in complex with NK-1.8k and indications for the development of antienterovirus protease inhibitor. Yaxin Wang, Lin Cao, Yangyang Zhai, Zheng Yin, Yuna Sun*,Luqing Shang*. Antimicrob. Agents. Chemother. 2017, 61, e00298-17.

11. Inhibition of enterovirus 71 replication by ana-hydroxy-nitrile derivative NK-1.9k. Yaxin Wang, Lin Cao, Yangyang Zhai, Jiaming Ma, Quandeng Nie, Ting Li, Zheng Yin, Yuna Sun*,Luqing Shang*. Antiviral Res. 2017, 141, 91-100.

12. Discovery of 2’-a-C-Methyl-2’-b-C-fluorouridine phosphoramidate prodrugs as inhibitors of Hepatitis C virus. Debin Zeng, Rui Zhang, Quandeng Nie, Lin Cao,Luqing Shang*, Zheng Yin* ACS Med. Chem. Lett. 2016, 7 (12), 1197-1201

13. Structure activity relationship study of peptidomimetic aldehydes as enterovirus 71 3C protease inhibitors. Yangyang Zhai, Yuying Ma, Fei Ma, Quandeng Nie, Xuejiao Ren, Yaxin Wang,Luqing Shang*, Zheng Yin*. Eur. J. Med. Chem. 2016, 124: 559-573.

14. A 3,7-dihydroxyphenoxazine-based fluorescent probe for selective detection of intracellular hydrogen peroxide. Zhiqiang Han Xiao Liang, Xuejiao RenLuqing Shang*, Zheng Yin*. Chem-Asian J. 2016, 11: 818-822.

15. Synthesis and structure–activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors. Debin Zeng, Yuying Ma, Rui Zhang, Quandeng Nie, Zhengjie Cui, Yaxin Wang,Luqing Shang*, Zheng Yin*. Bioorg.Med.Chem. Lett., 2016, 26 (7):1762-1766.

16. The discovery of indole derivatives as novel hepatitis C virus inhibitors.Zhiqiang Han, Xiao Liang, Yaxin Wang, Jie Qing, Lin Cao,Luqing Shang*, Zheng Yin*. Euro. J. Med. Chem., 2016, 116: 147-155.

17. Cyanohydrin as an anchoring group for potent and selective inhibitors of Enterovirus 71 3C protease. Yangyang Zhai, Xiangshuai Zhao, Zhengjie Cui, Man Wang, Yaxin Wang, Linfeng Li, Qi Sun, Xi Yang, Debing Zeng, Ying Liu, Yuna Sun, Zhiyong Lou,Luqing Shang*, Zheng Yin*, J. Med. Chem., 2015,58,941-9420.

18. Site-specific chemical modification of peptide and protein by thiazolidinediones. Peng Wang,Shumei Zhang,Qiuyue Meng,Ying Liu,Luqing Shang*, andZheng Yin*,Org. Lett., 2015, 17 (6), 1361–1364.

19. Biochemical characterization of recombinant Enterovirus 71 3C protease with fluorogenic model peptide substrates and development of a biochemical assay.Luqing Shang, Shumei Zhang, Xi Yang, Jixue Sun, Linfeng Li, Zhengjie Cui, Qiuhong He, Yu Guo, Yuna Sun*, Zheng Yin*, Antimicrob. Agents. Chemother., 2015 Apr; 59(4):1827-1836.

授权专利：

1.尚鲁庆,娄智勇，王亚鑫，饶子和等。核苷类化合物在制备治疗肠病毒71（EV71）感染疾病药物的应用。专利号：ZL. 201010613121.5。

2.尚鲁庆,赵向帅，娄智勇，王亚鑫，徐梦莹，王朋，崔璨璨，陈成，赵强，周红刚，饶子和等。抗肠病毒71（EV71）己内酰胺醛类化合物及其制备方法和用途。专利号：ZL.201110384897.9。

3.尚鲁庆,赵向帅，娄智勇，王亚鑫，徐梦莹，王朋，崔璨璨，陈成，赵强，周红刚，饶子和等。抗肠病毒71（EV71）己内酰胺类化合物及其制备方法和用途。专利号：ZL201110402922.1。

4.尚鲁庆，王朋，张雪，李林锋等。石蒜碱类化合物在制备抗肿瘤药物的应用。专利号：ZL. 201210063482.6。

5.张雪，尚鲁庆，崔璨璨等。抗登革热病毒（DENV）杂环肽类化合物及其制备方法和用途。专利号：ZL. 201210144172.7。