Single-molecule tracking-based drug screening

Abstract

AbstractThe single-molecule tracking of transmembrane receptors in living cells has provided significant insights into signaling mechanisms, such as mobility and clustering upon their activation/inactivation, making it a potential screening method for drug discovery. Using an automated system for large-scale single-molecule analysis, we screened for epidermal growth factor receptor (EGFR) from 1,134 of FDA approved drugs. Included in the hit 18 compounds covered all EGFR-targeted tyrosine kinase inhibitors in the library that suppressed phosphorylation-dependent mobility shift of EGFR, proving the concept of this approach. The remaining hit compounds are not reported as EGFR-targeted drugs and affected the mobility and/or clustering of EGFR to prevent EGFR-dependent cell growth. Thus, single-molecule tracking provides a new modality for discovering novel therapeutics on various receptor functions with previously untargeted mechanisms.