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P22077 is a cell permeable inhibitor of the ubiquitin-specific protease USP7 (IC50=8.6 µM), and the closely related deubiquitinase (DUB) USP47. P22077 showed weak or no inhibition (EC50 >50µM) towards a panel of 14 isopeptidases and other proteases. Treatment of cells with P22077 (20–40 µM) causes an accumulation of K48-linked ubiquitinated species, and down regulation of the USP7 targets HDM2 and claspin.