YAO Shao Qin

YAO Shao Qin

Professor

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Research

ORCID: 0000-0003-4715-769X
ResearcherID: B-8825-2008 

 

Recognition and Achievements

• Member of the International Scientific Advisory Board, Angewandte Chemie
• Dean’s Chair Professor, National University of Singapore, 2009-2012
• ASAIHL-Scopus Young Scientist Award, International, 2008
• Outstanding Scientist Award, Faculty of Science, National University of Singapore, 2007
• Mr & Mrs Sun Chan Memorial Award, International, 2006
• Young Research Award, NUS, 2005
• Young Investigator Award, A*STAR Singapore, 2002

 

Research Interests

Chemical biology and medicinal chemistry. We are interested in developing powerful strategies in Chemical Biology and Chemical Proteomics that enable organism-wide, high-throughput studies of enzymes, e.g. the so-called “catalomics”.

 

Research Highlight

Ref. Sun, J.; Gu, M.; Peng, L.; Guo, J.; Chen, P.; Wen, Y.; Feng, F.; Chen, X.; Liu, T.; Chen, Y.; Lu, X.; Gao, L.; Yao, S. Q.; Yuan, P. A Self-Assembled Nano-Molecular Glue (Nano-mGlu) Enables GSH/H₂O₂-Triggered Targeted Protein Degradation in Cancer Therapy. J. Am. Chem. Soc. 2025, in press.

Molecular glues are promising protein-degrading agents that hold great therapeutic potential but face significant chal-lenges in rational design, effective synthesis, and precise targeting to tumor sites. In this study, we first overcame some of these limitations by introducing a fumarate-based molecular glue handle onto specific ligands of therapeutic kinases (TBK1, FGFR, and Bcr-Abl), resulting in effective degradation of these important cancer targets. Despite broad applicabil-ity of the strategy, we unexpectedly discovered potent and widespread cytotoxicity across various cell lines including noncancerous ones, rendering it less effective in cancer therapy. To address this critical issue, we next developed a self-assembled nanoparticle-based molecular glue (nano-mGlu) on the basis of one of the newly discovered Bcr-Abl-degrading molecular glue (H1-mGlu). We showed the resulting nano-mGlu (named Cle-NP) was able to release H1-mGlu in vitro, in the presence of a high concentration of GSH or H₂O₂ (commonly found in tumor microenvironment). Subsequent in vivo studies with a K562-xenografted mouse model indicated Cle-NP was highly effective in tumor-specific degradation of endogenous Bcr-Abl expressed in K562 cells, leading to eventual tumor regression while maintaining good biosafety profiles. With key advantages of generality in molecular glue design, targeted delivery, potent antitumor activity partially induced by target-specific degradation, and minimized collateral damage to healthy tissues, our self-assembled nano-mGlu strategy thus provides a novel approach that might hold significant prom-ises for effective and personalized cancer therapy.

Representative Publications   

• Tang, G.; Wang, X.; Huang, H.; Xu, M.; Ma, X.; Miao, F.; Lu, X.; Zhang, C.-J.; Gao, L.; Zhang, Z.-M.; Yao, S. Q. Small Molecule-Induced Posttranslational Acetylation of Catalytic Lysine of Kinases in Mammalian Cells. J. Am. Chem. Soc. 2024, 146, 23978–23988.
• Wang, X.; Sun, J.; Huang, H.; Tang, G.; Chen, P.; Xiang, M.; Li, L.; Zhang, Z.-M.; Gao, L.; Yao, S. Q. Kinase Inhibition via Small Molecule-Induced Intramolecular Protein Cross-Linking. Angew. Chem. Int. Ed. 2024, 63, e202404195.
• Tang, G.; Wang, W.; Zhu, C.; Huang, H.; Chen, P.; Wang, X.; Xu, M.; Sun, J.; Zhang, C.-J.; Xiao, Q.; Gao, L.; Zhang, Z.-M.; Yao, S. Q. Global Reactivity Profiling of the Catalytic Lysine in Human Kinome for Development of Potential Targeted Covalent Inhibitors. Angew. Chem. Int. Ed. 2024, 63, e202316394.
• Zhang, B.; Brahma, R. K.; Zhu, L.; Feng, J.; Hu, S.; Qian, L.; Du, S.; Yao, S. Q.; Ge, J. Insulin-Like Growth Factor 2 (IGF2)-Fused Lysosomal Targeting Chimeras for Degradation of Extracellular and Membrane Proteins. J. Am. Chem. Soc. 2023, 145, 24272–24283.
• Qian, L.; Lin, X.; Gao, X.; Khan, R. U.; Liao, J.-Y.; Du, S.; Ge, J.; Zeng, S.; Yao, S. Q. The Dawn of a New Era: Targeting the ‘Undruggables’ with Antibody-Based Therapeutics. Chem. Rev. 2023, 123, 7782–7853.
• Qin, J.; Guo, J.; Tang, G.; Li, L.; Yao, S. Q. Multiplex Identification of Post-translational Modifications by Deep Learning-Assisted Photonic Crystal Hydrogel Sensors. Angew. Chem. Int. Ed. 2023, 62, e202218412.
• Chen, P.; Tang, G.; Zhu, C.; Sun, J.; Wang, X.; Xiang, M.; Huang, H.; Wang, W.; Li, L.; Zhang, Z.-M.; Gao, L.; Yao, S. Q. 2-Ethynylbenzaldehyde (EBA)-Based, Lysine-Targeting Irreversible Covalent Inhibitors for Protein Kinases and Non-Kinases. J. Am. Chem. Soc. 2023, 145, 3844–3849.