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Overview
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Background
Description:IC50: 8.6 nM (singleplexed); 7.8 nM (multiplexed)USP7, also known as HAUSP, has been found to be critical in cancer progression due to its influence on the stability of the tumor suppressor p53. P022077 Inhibits ubiquitin-specific protease (USP) 7 and also inhibits the closely related deubiquitinase (DUB) USP4. In vitro: P022077 had negligible activity versus DEN1 and SENP2core over the concentration range tested, but inhibited USP7 with an IC50 of 8 μM [1]. In another study Inhibiting, USP7 with the small-molecule inhibitor P22077 attenuates the p53-dependent apoptotic pathway by destabilizing Tip60. P22077, however, is still cytotoxic, and this is partly due to destabilization of Tip60 [2]. In vivo: P022077 is currently in in-vitro investigation and no animal in vivo study is ongoing. Clinical trial: P022077 is currently in the preclinical development and no clinical trial is ongoing.
[1] Tian X, Isamiddinova NS, Peroutka RJ, Goldenberg SJ, Mattern MR, Nicholson B, Leach C. Characterization of selective ubiquitin and ubiquitin-like protease inhibitors using a fluorescence-based multiplex assay format. Assay Drug Dev Technol. 2011;9(2):165-73.
[2] Dar A, Shibata E, Dutta A. Deubiquitination of Tip60 by USP7 determines the activity of the p53-dependent apoptotic pathway. Mol Cell Biol. 2013;33(16):3309-20.
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