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Biography

Dr. Mingliang Wang received his Ph.D. degree in medicinal chemistry from Fudan University in 2017, then he joined the laboratory of Professor Shaomeng Wang as a postdoc at University of Michigan, Ann Arbor. He returned to Shanghai Institute of Materia Medica, Chinese Academy of Science and was appointed to a faculty in 2021. Dr. Wang’s efforts mainly dedicate to the research of medicinal chemistry, his research work focuses on major clinical needs such as tumors and neurodegenerative diseases, design and synthesis of drug-like lead compounds, and lay solid foundation for the research and development of innovative drugs.

Research Directions

1. Discovery and optimization of small-molecule degraders based on proteolysis-targeting chimera (PROTAC) technology.

2. Targeting the key components of the ubiquitin-proteasome system--E3 ubiquitin ligases and deubiquitinating enzymes, design and synthesis of small-molecule modulators of E3 ubiquitin ligases and inhibitors of deubiquitinating enzymes.

3. Targeting the traditional “undruggable targets”, especially protein phosphatase and transcription factors with tumor immunotherapy effects, design and synthesis small-molecule inhibitors\degraders through new strategies for the development of anti-tumor drugs.

Achievements

1. Designed and synthesized a new type of allosteric inhibitors targeting SHP2 protein. This type of compounds can effectively inhibit the MAPK signaling pathway and YAP transcription activity, and also show good anti-tumor activity in vivo. First designed and synthesized a new type of degraders targeting SHP2 protein, and also the first reported degraders in PTP family.

2. Designed and synthesized a new type of E3 ubiquitin ligase cereblon (CRBN) ligands. The PROTACs designed and synthesized based on this type of ligands exhibit high-efficiency degradation activity in different targets and also have good drug-like properties.

3. Based on PROTAC technology, designed and synthesized small molecule degraders targeting the estrogen receptor (ERα), and the orally bioavailable estrogen receptor degraders have been initially achieved.

Publications

1. Qiqi Wu, Zhongya Sun, Zhifeng Chen, Jingqiu Liu, Hong Ding, Cheng Luo, Mingliang Wang* (共同通讯) , Daohai Du *., The discovery of a non-competitive GOT1 inhibitor, hydralazine hydrochloride, via a coupling reaction-based high-throughput screening assay., Bioorg. Med. Chem. Lett., 2022. https://doi.org/10.1016/j.bmcl.2022.128883

2. Shuai Mao^#, Yahao Zhao^#, Zixuan Luo^#, Ruizhe Wang, Bo Yuan, Jianping Hu, Linghao Hu, San-Qi Zhang, Xiaoxing Ye, Mingliang Wang*(共同通讯), Zhengkai Chen*., Metal-free photo-induced sulfidation of aryl iodide and other chalcogenation., Frontiers in Chemistry, 2022. DOI: 10.3389/fchem.2022.941016

3. Jiacheng Li^#, Ting Liu^#, Yuanli Song^#, Mingyu Wang, Liping Liu, Hongwen Zhu, Qi Li, Jin Lin, Hualiang Jiang, Kaixian Chen, Kehao Zhao, Mingliang Wang, Hu Zhou*, Hua Lin*, Cheng Luo*.Discovery of small-molecule degraders of the CDK9-cyclin T1 complex for targeting transcriptional addiction in prostate cancer., J. Med. Chem. 2022, 65(16):11034-11057.

4. Tonghai Liu, Wenjia Shi, Yiluan Ding, Qiqi Wu, Bei Zhang, Naixia Zhang, Mingliang Wang, Daohai Du, Hao Zhang, Bo Han, Dean Guo, Jie Zheng, Qi Li, Cheng Luo., (-)-Epigallocatechin Gallate is a Noncompetitive Inhibitor of NAD Kinase., ACS Med Chem Lett. 2022.

5. Yunfu Deng, Guangzhi Ma, Karin A. Vallega, Dongsheng Wang, Mingliang Wang, Changwei Wang, Shaomeng Wang, Suresh S. Ramalingam and Shi-Yong Sun., Therapeutic efficacy of the novel SHP2 degrader SHP2-D26,alone or in combination, against lung cancer is associated with modulation of p70S6K/S6, Bim and Mcl-1., Cancer Gene Ther (2022). https://doi.org/10.1038/s41417-022-00472-3

6. Mahesh P. Paudyal^#, Mingliang Wang (co-first author) ^#, Juha H. Siitonen, Yimin Hu，Muhammed Yousufuddin, Hong C. Shen^*, John R. Falck^*, László Kürti^*., Intramolecular N-Me and N-H Amino etherification for the Synthesis of N-Unprotected 3-Amino-O-Heterocycles. Org. Biomol. Chem., 2021, 19, 557-560. 

7. Guangya Zhu^#, Jingjing Xie^#, Zhenzhen Fu, Mingliang Wang, Qichen Zhang, Hao He, Zijun Chen, Xin Guo, Jidong Zhu*., Pharmacological inhibition of SRC-1 phase separation suppresses YAP oncogenic transcription activity, Cell Research., 2021,31,1028-1031.

8. Mingliang Wang^#, Jianfeng Lu^#, Mi Wang, Chao-Yie Yang, Shaomeng Wang^*., Discovery of SHP2-D26 as a First, Potent and Effective PROTAC Degrader of SHP2 Protein. J. Med. Chem. 2020, 63, 14, 7510-7528. Highlight as Feature Article and the first PTP family degrader.

9. Jiantao Hu#, Biao Hu#, Mingliang Wang (co-first author) #, Fuming Xu#, Bukeyan Miao#, Chaoyie Yang, Mi Wang, Zhaomin Liu, Daniel Hayes, Krishnapriya Chinnaswamy, James Delproposto, Jeanne Stuckey, Shaomeng Wang*., Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER). J. Med. Chem. , 2019, 62, 3, 1420-1443.

10. Mingliang Wang, Jilai Han, Xiaojia Si, Yimin Hu, Jidong Zhu* and Xun Sun*., Effective approach to ureas through organocatalyzed one-pot process. Tetrahedron Lett, 2018, 59, 1614-1618. 

11. Jingjing Xie^#, Xiaojia Si^#, Shoulai Gu, Mingliang Wang, Jian Shen, Haoyan Li, Jian Shen, Dan Li, Yanjia Fang, Cong Liu* and Jidong Zhu*., Allosteric inhibitors of SHP2 with therapeutic potential for cancer treatment. J. Med. Chem., 2017, 60, 10205-10219.

12. Mingliang Wang, Yanjia Fang, Shoulai Gu, Fangfang Chen, Zhengjiang Zhu, Xun Sun* and Jidong Zhu*., Discovery of novel 1,2,3,4-tetrahydrobenzo[4, 5]thieno[2, 3-c]pyridine  derivatives as potent and selective CYP17 inhibitors. Eur. J. Med. Chem., 2017, 132, 157-172.

13. Mingliang Wang, Yimin Hu, Zhe Jiang, Hong C. Shen* and Xun Sun*., Divergent Copper-mediated dimerization and hydroxylation of benzamides involving C-H bond functionalization., Org. Biomol. Chem., 2016, 14, 4239-4246.

14. Mingliang Wang, Xixi Liu, Lu Zhou, Jidong Zhu* and Xun Sun*., Fluorination of 2-substituted benzo[b]furans with Selectfluor?., Org. Biomol. Chem., 2015, 13, 3190-3193.