Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

Dr. ZHANG Xuan is a principal investigator and professor at Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Dr. ZHANG earned his Ph.D. in organic chemistry from East China Normal University under the supervision of Prof. Wei Lu in 2014. Between 2014-2018, he served as a postdoctoral fellow under the guidance of Prof. Guangrong Zheng at University of Arkansas for Medical Sciences. In 2018, Dr. ZHANG joined University of Florida as a postdoctoral associate and was promoted to a research assistant professor one year later. Dr. ZHANG has published over thirty original manuscripts in prestigious journals, including Nat. Med., Nat. Commun., Chem. Commun., J. Med. Chem, Eur. J. Med. Chem. Remarkably, DT2216, a first-in-class BCL-XL degrader disclosed in the Nature Medicine paper, is currently in the IND-enabling phase and expects to enter the clinical in 2021.

Education

2009.9 - 2014.7 Ph.D., Organic Chemistry, East China Normal University, Shanghai, China

2001.9 - 2005.6 B.S., Chemical Engineering, Shanghai Normal University, Shanghai, China

Work Experience

2020.12 - Present Professor, Shanghai Institute of Materia Medica, Chinese Academy of Sciences

2019.07 - 2020.12 Research Assistant Professor, College of Pharmacy, University of Florida

2018.06 - 2019.06 Postdoctoral Associate, College of Pharmacy, University of Florida

2014.12 - 2018.05 Postdoctoral Fellow, College of Pharmacy, University of Arkansas for Medical Sciences

2014.08 - 2014.11 Research Assistant, School of Chemistry and Molecular Engineering, East China Normal University

2005.07 - 2009.08 Research Fellow, Shanghai Institute of Material Medica, Chinese Academy of Sciences

Research Directions

1.The development of novel drug candidates utilizing targeted protein degradation (TPD) technology.

2.The discovery and mechanism studies of bioactive molecules targeting protein degradation pathway.

3.The development of small-molecule inhibitors of protein-protein interactions.

4.The discovery of novel senolytics for the treatment of aging-related diseases.

Grants & Research Projects

Achievements

Dr. Zhang’s previous research highlights the potential to use PROTAC technology to reduce on-target drug toxicities and rescue the therapeutic potential of previously undruggable targets. Remarkably, DT2216, a first-in-class BCL-XL degrader, is currently in the IND-enabling phase and expects to enter the clinical in 2021. (Nat. Med. 2019, 25, 1938-1947; Chem. Commun. 2019, 55, 14765-14768) In addition, another BCL-XL degrader called PZ227 effectively clears senescent cells and rejuvenates tissue stem and progenitor cells in naturally aged mice, highlighting the potential applications of protein degraders in the treatment of aging-related diseases. (Nat. Commun. 2020, 11, 1996) Moreover, in collaboration with Dr. Daiqing Liao at University of Florida, Dr. Zhang developed the first-in-class HDAC3-specific degraders, providing powerful tools to further investigate the biological roles of HDAC3 in living systems. (Chem. Commun. 2020, 56, 9866-9869)

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Social Titles

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Awards & Honors

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Pubilcations

Full Publication List

Selected Publications

1.Yufeng Xiao#, Jia Wang#, Lisa Y. Zhao, Xinyi Chen, Guangrong Zheng, Xuan Zhang*, Daiqing Liao*. Discovery of histone deacetylase 3 (HDAC3)-specific PROTACs. CHEMICAL COMMUNICATIONS, 2020, 56(68), 9866-9869. https://doi.org/10.1039/D0CC03243C

2.Yonghan He#, Xuan Zhang#, Jianhui Chang#, Ha-Neui Kim#, Peiyi Zhang, Yingying Wang, Sajid Khan, Xingui Liu, Xin Zhang, Dongwen Lv, Lin Song, Wen Li, Dinesh Thummuri, Yaxia Yuan, Janet S. Wiegand, Yuma T. Ortiz, Vivekananda Budamagunta, Jennifer H. Elisseeff, Judith Campisi, Maria Almeida, Guangrong Zheng*, Daohong Zhou*. Using proteolysis targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity. NATURE COMMUNICATIONS, 2020, 11(1), 1996. https://doi.org/10.1038/s41467-020-15838-0

3.Xuan Zhang#, Dinesh Thummuri#, Xingui Liu, Wanyi Hu, Peiyi Zhang, Sajid Khan, Yaxia Yuan, Daohong Zhou*, Guangrong Zheng*, Discovery of PROTAC BCL-XL Degraders as Potent Anticancer Agents with Low on-target Platelet Toxicity. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2020, 192, 112186. https://doi.org/10.1016/j.ejmech.2020.112186

4.Xuan Zhang#, Dinesh Thummuri#, Yonghan He, Xingui Liu, Peiyi Zhang, Daohong Zhou, Guangrong Zheng*. Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-XL. CHEMICAL COMMUNICATIONS, 2019, 55(98), 14765-14768. https://doi.org/10.1039/C9CC07217A

5.Sajid Khan#, Xuan Zhang#, Dongwen Lv#, Qi Zhang, Yonghan He, Peiyi Zhang, Xingui Liu, Dinesh Thummuri, Yaxia Yuan, Janet S. Wiegand, Jing Pei, Weizhou Zhang, Abhisheak Sharma, Christopher R. McCurdy, Vinitha M. Kuruvilla, Natalia Baran, Adolfo A. Ferrando, Yong-mi Kim, Anna Rogojina, Peter J. Houghton, Guangcun Huang, Robert Hromas, Marina Konopleva, Guangrong Zheng*, Daohong Zhou*. A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. NATURE MEDICINE, 2019, 25(12), 1938-1947. https://doi.org/10.1038/s41591-019-0668-z

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