The small molecule BI8626 inhibits HUWE1 in vitro by competing with protein substrates for ubiquitination. To assess whether BI8626 elicits global changes in protein stabilities consistent with HUWE1 inhibition, we performed quantitative proteomic analyses of HEK293 cells upon exposure to 15 µM BI8626 for 3 different durations. Analogous global proteomic analyses were performed to compare WT and HUWE1 knock-out HEK293 cells.