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FT709 is an inhibitor of ubiquitin-specific protease 9X (USP9X; IC50 = 82 nM).1 It is selective for USP9X over a panel of 20 deubiquitinases (IC50s = >25 µM for all). FT709 (10 µM) decreases the levels of the USP9X substrate centrosomal protein of 55 kDa (CEP55), as well as zinc-finger protein 598 (ZNF598), makorin 1 (MKRN1), and MKRN2, which are involved in the ribosomal quality control pathway, and inhibits the ribosomal stalling response to polyA tracts, a translation quality-control process, in a reporter assay using HEK293 cells.
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1. The deubiquitylase USP9X controls ribosomal stalling. J. Cell. Biol. 220(3), e202004211 (2021).