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In contrast to epoY, an epoxide inhibitor of VASH1/2-SVBP,9 parthenolide does not block VASH1-SVBP activity in vitro. Lastly, we show that epoY is an efficacious inhibitor of microtubule detyrosination in cells, providing an alternative chemical means to block detyrosination. Collectively, our work supports the notion that parthenolide is a promiscuous inhibitor of many cellular processes and suggests that its ability to block detyrosination may be an indirect consequence of reducing the polymerization-competent pool of tubulin in cell