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Active site-targeted covalent irreversible inhibitors of USP7 impair the functions of Foxp3+ T-regulatory cells by promoting ubiquitination of Tip60

Fig 1

P217564 is a second generation USP7 inhibitor with increased potency that retains selectivity.

(A) Schematic representation of Ub- EKL isopeptidase reporter assay: cleavage by the isopeptidase at the carboxy-terminal glycine of the Ub releases catalytically active EKL, which liberates a quantifiable fluorescent product in the presence of its substrate. (B) P217564 demonstrates potent and specific inhibition of USP7 versus other purified DUBs and proteases.

Fig 1

doi: https://doi.org/10.1371/journal.pone.0189744.g001