Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

Dr. ZHAO obtained his bachelor degree from Suzhou University and a Ph.D degree in Organic Chemistry from Nanyang Technological University (Singapore) under the supervision of Prof. Teck-Peng Loh. He completed postdoc training in Prof. Shaomeng Wang’s lab at University of Michigan Ann Arbor from 2009 to 2015, and he contributed to the nomination of SAR405838 as a potent MDM2 inhibitor that entered human clinical trials. Since March 2015, Dr. ZHAO started his independent research at Shanghai Institute of Materia Medica and served as a Professor and Principal Investigator. His current research focuses on discovery potent small molecules modulating novel drug targets.

Education:

1999.9-2003.6 Soochow University, Jiangsu Province, P. R. China, B.S. in Chemistry Education

2003.8-2005.5 National University of Singapore, Ph.D. candidate in Organic Chemistry

2005.6-2009.1 Nanyang Technological University, Singapore, Ph.D. in Organic Chemistry

Work Experience:

2008.6-2009.5 Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore. Project Officer

2009.6-2015.3 Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. Postdoctoral Research Fellow

2015.3-current Shanghai Institute of Materia Medica, Shanghai, China, Professor and Principal Investigator

Research Directions

1. Modulation of protein-protein interactions with rational designed small molecules;

2. Discovery and biological activity studies of novel kinase inhibitors;

3. Modifications and medicinal chemistry studies of natural products with biological activities.

Grants & Research Projects

1.National Natural Science Foundation of China, Grants 82073682, Principal Investigator , 2021/01 to 2024/12;

2.National Natural Science Foundation of China, Grants 81872724, Principal Investigator , 2019/01 to 202212;

3.Science and Technology Commission of Shanghai Municipality, Grant 18431907100, co-PI, 2019/01-2021/12.

Achievements

1.Discovery of a selective NIK kinase inhibitor XT2: our data show that small molecule NIK inhibitor XT2 inhibited that activation of NFκB2 signal pathway in liver cells, decreased the liver cells apoptosis induced by toxin, and prolonged the life span of mice in a liver-damage model. These results suggest that inhibition of NIK activity in vivo maybe a good therapeutic target for treating liver-damage related diseases.

2.Discovery of small molecule BY27 that blocks BET bromodomain/Histone protein-protein interactions: our data demonstrated significant differences between a selective BET BD2 inhibitor and a pan BET inhibitor, which suggest that selective BET BD2 inhibitors have potential pharmaceutical applications in clinical setting.

3.Discovery of a selective ASK1 kinase inhibitor YD57: our data show that YD57 inhibited ASK1 and several other kinases, which promoted apoptosis, induced cell cycle arrest, and had very potent activities in killing liver cancer cells.

4.Discovery of EGFR kinase inhibitors: we found that the allenamide moiety was a good bioisostere of the acrylamide group in structures of covalent EGFR inhibitors. The allenamide moiety reacted with the -SH group of a cysteine much faster than that of the acrylamide group. These data suggest the allenamide moiety could be used for labeling the -SH group of cysteines in vitro and in intact cells.

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Social Titles

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Awards & Honors

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Pubilcations

Full Publication List

Selected Publications

1.Jing Cheng, Xuexin Feng, Zhiqiang Li, Feilong Zhou, Jin-Ming Yang, Yujun Zhao*, Pharmacological inhibition of NF-κB-Inducing Kinase (NIK) with small molecules for the treatment of human diseases, RCS Medicinal Chemistry, 2021, DOI: 10.1039/d0md00361a.

2.Xuan Wang, Jiaxiang Liu, Ziqin Yan, Xiaohong Liu, Sixiu Liu, Yanrui Suo, Weiwei Lu, Jinfeng Yue, Kaixian Chen, Hualiang Jiang, Yujun Zhao*, Mingyue Zheng*, Dongcheng Dai*, Xiaojie Lu*, Diversified strategy for the synthesis of DNA-encoded oxindole libraries, Chemical Science, 2021, DOI: 10.1039/D0SC06696F.

3.Zhiqiang Li, Xinzhi Li, Ming-Bo Su, Li-Xin Gao, Yu-Bo Zhou, Bingchuan Yuan, Xilin Lyu, Ziqin Yan, Chujiao Hu, Hao Zhang, Cheng Luo, Zheng Chen*, Jia Li*, Yujun Zhao*, Discovery of a potent and selective NF-κB-inducing kinase (NIK) inhibitor that has anti-inflammatory effects in vitro and in vivo, Journal of Medicinal Chemistry, 2020, 63, 4388-4407.

4.Shiyan Zhang, Chaoying Huang, Xilin Lyu, Peipei Wang, Yi Zang, Zengtao Wang, Huan Wang, Jia Li*, Yujun Zhao*, Discovery of a 2-pyridinyl urea-containing compound YD57 as a potent inhibitor of apoptosis signal -regulating kinase 1 (ASK1), European Journal of Medicinal Chemistry, 2020, 195, 112277.

5.Deheng Chen, Tian Lu, Ziqin Yan, Wenchao Lu, Feilong Zhou, Xilin Lyu, Biling Xu, Hualiang Jiang, Kaixian Chen, Cheng Luo*, and Yujun Zhao*, Discovery, structural insight, and bioactivities of BY27 as a selective inhibitor of the second bromodomains of BET proteins, European Journal of Medicinal Chemistry, 2019, 182, 111633.

6.Erbao Zhao, Feilong Zhou, and Yujun Zhao*, Lewis Acids Promoted 3+2 Cycloaddition of Oxaziridines and Cyclic Allylic Alcohols through Carbonyl Imine Intermediates, Journal of Organic Chemistry, 2019, 84 (7), 4282–4293.

7.Deheng Chen, Dexiang Guo, Ziqin Yan, Yujun Zhao*, Allenamide as a bioisostere of acrylamide in design andsynthesis of targeted covalent inhibitors Med. Chem. Commun. 2018, 9, 244-253.

8.Feilong Zhou, Erbao Zhao, Ziqin Yan, Deheng Chen, Yujun Zhao*, Synthesis of 3,4-diarylsubstituted hexahydro-1H-indoles, Tetrahedron Letters, 2018, 59, 1871-1874.

9.Xiaomeng Ren, Xinzhi Li, Linna Jia, Deheng Chen, Hai Hou, Liangyou Rui, Yujun Zhao*, Zheng Chen*, A small-molecule inhibitor of NF-kB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury, FASEB Journal. 2017, 2, 711-718.

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