Email: Zhenyi.Hu@sioc.ac.cn
Phone:
Office: 100 Haike Rd, #13,
Website:
2023-present, PI, Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute ofOrganic
Chemistry, Chinese Academy of Sciences
2018-2023, PostDoc, Yale University
2013-2018, Ph.D., University of Colorado at Boulder
2012-2013, Research assistant, Tsinghua University
2009-2012, M.Sc., Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS)
2005-2009, B.Sc., China Pharmaceutical University
Dr. Hu earned his Ph.D. from the University of Colorado Boulder under the mentorship of Professor Hang Yin. During his postdoctoral studies, he worked with the founder of PROTAC technology, Professor Craig Crews, at Yale University, with collaborative guidance from Professor Yansheng Liu. Dr. Hu focuses on the field of medicinal chemistry and chemical biology, with a research emphasis on autoimmune diseases and cancer.
In the realm of developing small molecule inhibitors for crucial proteins, Dr. Hu has accumulated significant expertise. He pioneered the development of an efficient TLR8 small molecule inhibitor through methods like structure-based rational design. This TLR8 inhibitor has gained international, U.S., and Chinese patents, and the patents have been transferred. It has received IND approvals from the NMPA and U.S. FDA and is currently undergoing clinical trials.
Moreover, Dr. Hu has innovatively developed a new generation of dual-functional small molecule inhibitors targeting protein phosphorylation, named PhosTAC. Compared to traditional kinase inhibitors, PhosTAC boasts advantages such as high efficiency, precision, and specificity. Serving as a novel and versatile platform technology for drug development, PhosTAC holds broad potential applications.
The Hu research group in Medicinal Chemistry and Chemical Biology is dedicated to investigating and controlling life processes through chemical means. Focused on bifunctional molecules (such as PROTAC, PhosTAC), the group utilizes chemical synthesis as a tool (Biology driven, chemistry empowered) to engineer life and regulate the onset of diseases. Their objective is to develop therapeutic approaches for conditions like Alzheimer's disease and cancer based on bifunctional molecular drugs.
1. Hu, Z.#; Chen, P.#; Li, W.; Douglas, T.; Hines, J.; Liu, Y.; Crews, C.; Targeted Dephosphorylation of Tau by Phosphorylation Targeting Chimeras (PhosTACs) as a Therapeutic Modality. Journal of the American Chemical Society. 2023, 145, 7, 4045–4055
2. Zhang, S.#; Hu, Z.#; Tanji, H.; Jiang, S.; Das, N.; Li, J.; Sakaniwa, K.; Jin, J.; Bian, Y.; Ohto, U.; Shimizu, T.; Yin, H.; Inhibition of Toll-like Receptor 8 through stabilization of its resting state. Nature Chemical Biology. 2018, 14, 58-64 (cover article)
3. Hu, Z.; Tanji, H.; Koo, K.; Chan, J.; Zhang, S.; Candia, A.; Shimizu, T.; Yin, H.; Small-molecule TLR8 antagonists via structure-based rational design. Cell Chemical Biology. 2018, 25, 1286–1291 (cover article)
4. Hu, Z.; Crews, C.; Recent Developments in PROTAC-Mediated Protein Degradation: From Bench to Clinic. Chembiochem. 2022, 23 (2), e202100270.
5. Chen, P. #; Hu, Z. #; An, E.; Okeke, I.; Zheng, S.; Lo, X.; Gong, A.; Jaime-Figueroa, S.; Crews, C.; Modulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs). ACS Chemical Biology. 2021, 16, 12, 2808–2815.
6. Hu, Z.; Zhang, T.; Jiang, S.; Yin, H.; Protocol for evaluation and validation of TLR8 antagonists in HEK-Blue cells via secreted embryonic alkaline phosphatase assay. Cell Star Protocols. 2022,3, 101061.
7. Samarasinghe, K.; Jaime-Figueroa, S.; Burgess, M.; Nalawansha, D.; Dai, K.; Hu, Z.; Bebenek, A.; Holley, S.; Crews, C.; Targeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras. Cell Chemical Biology. 2021, 28(5): 648-661 e645.
8. Hany, Z.; Meas, H.; Haug, M.; Beckwith, M.; Louet, C.; Ryan, L.; Hu, Z.; Landskron, J.; Nordbo, S.; Tasken, K,; Yin, H.; Damas, J.; Flo. T.; Sensing of HIV-1 by TLR8 activates human T cells and reverses latency. Nature Communication. 2020 Jan 9;11(1):147
9. Xia, T.; Hu, Z.; Ji, W.; Zhang, S.; Shi, H.; Liu, C.; Pang, B.; Liu, G.; Liao, X.; Synthesis of Withasomnine and Pyrazole derivatives via intramolecular dehydrogenative cyclization, as well as biological evaluation of Withasomnine-based scaffolds. Organic Chemistry Frontiers. 2018,5, 850-854
10. Moen,S.; Ehrnstrom, B.; Kojen, J.; Yurchenko, Beckwith, K.; Afset, J.; Damas,J.; Hu, Z.; Yin, H.; Espevik, T.; Stenvik, J.; Human Toll-like Receptor 8 (TLR8) is an important sensor of pyogenic bacteria, and is attenuated by cell surface TLR signaling. Frontier in Immunology.10:1209.
11. Ehrnstrom, B.; Kojen, J.F.; Moen, S.H.; Hu, Z.; Damas, J.K., Mollnes, T.E.; Yin, H.; Espevik, T.; Stenvik J.; TLR8 and complement C5 induce cytokine release and thrombin activation in human whole blood challenged with Gram-positive bacteria. Journal of Leukocyte Biology 2020, 107, 673–683.
12. Chen, H.#; Hu, Z.#; Tang, C.; Quinn, R.; Feng, Y.; Yao, S.; Ye Y.; Dictamins A–C, three unprecedented apotirucallane-type trinortriterpenoids from Dictamnus dasycarpus.Tetrahedron Letters. 2013, 5, 4150–4153
13. Qi X.; Wang, L.; Zhu, J.; Hu, Z.; Zhang, J.; Self-double-emulsifying drug delivery system (SDEDDS): A new way for oral delivery of drugs with high solubility and low permeability. International Journal of Pharmaceutics. 2011, 409, 245–251.
# Co-First Author.