Expression proteomics reveals protein targets and highlights mechanisms of action of small molecule drugs

Abstract

Phenomenological screening of small molecule libraries for anticancer activity yields potentially interesting candidate molecules, with a bottleneck in the determination of drug targets and the mechanism of anticancer action. A novel approach to drug target deconvolution compares the abundance profiles of proteins expressed in a panel of cells treated with different drugs, and identifies proteins with cell-type independent and drug-specific regulation that is exceptionally strong in relation to the other proteins. Mapping top candidates on known protein networks reveals the mechanism of drug action, while abundant proteins provide a signature of cellular death/survival pathways. The above approach can significantly shorten drug target identification, and thus facilitate the emergence of novel anticancer treatments.Comment: 26 pages, 3 figures, 3 supplementary figures. Raw mass-spectrometry files were deposited to chorusproject.org. Supplementary tables and figures available upon reques