qHTS to Identify Substrates of P-glycoprotein (P-gp) and Collateral Sensitivity agents of P-gp-expressing Cancer Cells

National Center For Advancing Translational Sciences

Investigators

Abstract

NCGC is aiming to identify P-gp substrates within its libraries to provide early filters of P-gp transport potential, as well as developing compounds capable of selectivity killing P-gp expressing cells (as anticancer agents). During this period, the project team developed a series of high-throughput assays to examine differential toxicity between drug-naive cancer cell lines and P-gp-overexpressing drug-selected sublines. To identify P-gp substrates, high-throughput screens were performed against annotated libraries, which included a comprehensive collection of clinically approved drugs, probe small molecules with known mechanisms of action, and experimental therapeutics designed to modulate a wide range of targets.