Chemical Biology Approaches in Drug Target Discovery: From Affinity Probes to Thermal Stability Analysis
Main Article Content
Keywords
chemical biology, drug target discovery, affinity probe, thermal stability analysis, ABPP, AfBPP, DARTS, CETSA, TPP
Abstract
Drug target discovery is a critical step in new drug research and development, and chemical biology techniques and theories provide powerful tools to advance this process. This review summarizes two major categories of drug target discovery methods—affinity probes and thermal stability analysis—and their recent research progress, highlighting the role of chemical biology approaches. It also aims to deepen the author’s understanding of future directions for advanced study in chemical biology. The review focuses on activity-based protein profiling (ABPP) and affinity-based protein profiling (AfBPP) as representative affinity probe technologies, as well as label-free thermal stability techniques including DARTS, CETSA, and TPP, with extensions to related developments. Both categories of drug target discovery technologies have distinct advantages, and their combined use enables a complete workflow from theory to practice and from discovery to validation. Chemical biology methods play a positive role in drug target identification.
References
- [1] Chen, J. S., Zhang, X. Y., Liu, J. H., Meng, W. Q., & Zhang, L. (2023). Progress in the application of activity-based and affinity-based protein expression profiling in pharmacological and toxicological research. Chinese Journal of Pharmacology and Toxicology, 37(12), 951-958.
- [2] Zhang, M. T., & Ding, M. (2023). Application of chemical proteomics technology in drug target identification. Life Sciences, 35(06), 816-823. https://doi.org/10.13376/j.cbls/20230006
- [3] Li, Y. Z., Wan, N., & Ye, H. (2025). Breakthroughs in target discovery and application of photoaffinity probes in chemical proteomics. Chinese Journal of Modern Applied Pharmacy, 42(23), 4184-4190. https://doi.org/10.13748/j.cnki.issn1007-7693.20250955
- [4] Lü, J. W., & Ye, M. L. (2021). Research progress on label-free drug target identification proteomics methods. Journal of Mass Spectrometry, 42(05), 845-861.
- [5] Chen, Y. J., Jiang, W. W., Li, L. H., Zhang, C. Z., Zhang, C., & Jia, D. (2022). Identification of direct binding target proteins of sodium danshensu based on DARTS technology. Pharmaceutical and Clinical Research, 30(01), 58-61+65. https://doi.org/10.13664/j.cnki.pcr.2022.01.007
- [6] Chen, F. Y., Qin, W., Li, R. M., Cheng, Y., Zhu, Z., Chen, L., & Zhao, Y. N. (2022). Discovery and confirmation of the brain protein action site AK1 of ginsenoside based on DARTS technology. China Journal of Chinese Materia Medica, 47(05), 1336-1342. https://doi.org/10.19540/j.cnki.cjcmm.20211117.703
- [7] Liu, Z. Y., Zhu, S. B., Deng, H. T., & Chen, Y. L. (2021). Identification of target proteins of TH588 by thermal proteomics analysis. Journal of Mass Spectrometry, 42(05), 951-961.
- [8] Rao, Q. L., Xu, Y. T., Chen, H., Huang, Z. X., Zhang, G., Lü, J. R., ... & Deng, X. Q. (2025). Study on the mechanism of action and potential new effects of Erigeron breviscapus extract in treating encephalopathy based on thermal proteomics technology. Modern Chinese Medicine, 27(03), 460-471. https://doi.org/10.13313/j.issn.1673-4890.20241111001
- [9] Dong, H., Yang, X., Wang, P., et al. (2025). Identification and verification of methylenetetrahydrofolate dehydrogenase 1-like protein as the binding target of natural product pseudolaric acid A. Natural Products and Bioprospecting, 15, 21. https://doi.org/10.1007/s13659-025-00502-1
- [10] Tang, Z. H., & Liu, X. Y. (2025). A new method for studying small molecule-protein interactions—PELSA. Journal of Mass Spectrometry, 46(01), 1-2.
Article Sidebar
This work is licensed under a Creative Commons Attribution 4.0 International License.