biostudies-literatureCheng LJohn S. Dunn FoundationNIAID NIH HHSU.S. Department of DefenseNational Cancer InstituteNCI NIH HHSWelch FoundationNational Institutes of HealthNIAIDNational Institute of General Medical SciencesCancer Prevention and Research Institute of TexasNIGMS NIH HHS428-445https://www.ebi.ac.uk/biostudies/studies/S-EPMC10960704biostudies-literatureUnknown31(3)Recent years have seen a remarkable growth in the field of protein-based medical treatments. Nevertheless, concerns have arisen regarding the cytotoxicity limitations, low affinity, potential immunogenicity, low stability, and challenges to modify these proteins. To overcome these obstacles, proximity-induced chemistry has emerged as a next-generation strategy for advancing protein therapeutics. This method allows site-specific modification of proteins with therapeutic agents, improving their effectiveness without extensive engineering. In addition, this innovative approach enables spatial control of the reaction based on proximity, facilitating the formation of irreversible covalent bonds between therapeutic proteins and their targets. This capability becomes particularly valuable in addressing challenges such as the low affinity frequently encountered between therapeutic proteins and their targets, as well as the limited availability of small molecules for specific protein targets. As a result, proximity-induced chemistry is reshaping the field of protein drug preparation and propelling the revolution in novel protein therapeutics.Cell chemical biologyAdvancing protein therapeutics through proximity-induced chemistry.PMC10960704R01 AI165079R35-GM133706R01-AI165079R01-CA277838R21 CA255894W81XWH-21-1-0789R01 CA277838R21-CA255894HT9425-23-1-0494C-1970R35 GM133706Zhang SSGuo YXiao HCheng LWang YfalseAdvancing protein therapeutics through proximity-induced chemistry.Recent years have seen a remarkable growth in the field of protein-based medical treatments. Nevertheless, concerns have arisen regarding the cytotoxicity limitations, low affinity, potential immunogenicity, low stability, and challenges to modify these proteins. To overcome these obstacles, proximity-induced chemistry has emerged as a next-generation strategy for advancing protein therapeutics. This method allows site-specific modification of proteins with therapeutic agents, improving their effectiveness without extensive engineering. In addition, this innovative approach enables spatial control of the reaction based on proximity, facilitating the formation of irreversible covalent bonds between therapeutic proteins and their targets. This capability becomes particularly valuable in addressing challenges such as the low affinity frequently encountered between therapeutic proteins and their targets, as well as the limited availability of small molecules for specific protein targets. As a result, proximity-induced chemistry is reshaping the field of protein drug preparation and propelling the revolution in novel protein therapeutics.2024-01-01T00:00:00Z2024 Mar2026-06-02T07:15:49.882Z2025-04-05T12:38:28.829ZS-EPMC109607043780207610.1016/j.chembiol.2023.09.004