P5091(P005091) is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with EC50 of 4.2 M and the closely related USP47.P5091 is a trisubstituted thiophene with dichlorophenylthio, nitro, and acetyl substituents mediating anti-USP7 activity. P5091 exhibits potent, specific, and selective deubiquitylating activity against USP7. In contrast, P5091 does not inhibit other DUBs or other families of cysteine proteases tested (EC50 > 100 mM). P5091 inhibits the labeling of USP7 with HA-UbVME in a concentration-dependent manner. USP7-mediated cleavage of high molecular weight polyubiquitin chains is inhibited in a dose-dependent manner by P5091.
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