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Abstract Graphical abstract Chemical proteomics is widely applied in small molecule target identification. However, in general it does not identify non‐protein small molecule targets, and thus, alternative methods for target identification are in high demand. We report the discovery of the autophagy inhibitor autoquin, and the identification of its molecular mode of action using image‐based morphological profiling in the cell painting assay.
Highlights • Identification of a structurally novel inhibitor of the UNC119-Src interaction • Impairment of UNC119-medicated Src plasma membrane enrichment • Reduction of activating Src Y416 autophosphorylation • Reduction of growth and clonogenic potential of Src-dependent cells Summary Interference with the signaling activity of the N-myristoylated nonreceptor protein tyrosine kinase Src is considered a viable approach in anti-cancer drug discovery.
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