Solvent-induced partial cellular fixation decodes proteome-wide drug targets and downstream pathways in living cells.

ABSTRACT: Comprehensive knowledge of drug targets, their binding efficacy, and the subsequent activated cellular pathways is critical for determining therapeutic efficacy, elucidating mechanisms of action, and identifying potential side effects. However, acquiring this information in living cells remains challenging using routine proteomics methods. In this study, we propose an approach, the Solvent-Induced partial Cellular Fixation Approach (SICFA), to assess protein stability and drug interactions in living cells. By combining SICFA with quantitative proteomics, we can quantify stability for approximately 5600 proteins within the intracellular proteome. SICFA demonstrates high sensitivity in detecting drug-induced stability changes in target proteins and downstream effector proteins. Time-resolved

SUBMITTER: Yu T 

PROVIDER: S-EPMC12647918 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature