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Overview
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Background
P005091 is a selective, potent inhibitor of USP7 deubiquitylating activity, which is demonstrated to downregulate claspin and phosphorylation of the DNA checkpoint kinase Chk1, and to synergize with genotoxic agents. USP7, known as herpes-associated-ubiquitin-specificprotease (HAUSP), is a deubiquitylating enzyme that regulates the levels of the oncoprotein HDM2 and its substrate, the tumor suppressor p53. P005091 accelerated the degradation of HDM2, while analogs of the compound induced dose- and time-dependent increases in the protein levels of p53 and p21.What’s more,P005091 induced apoptosis in numerous cancer cell lines, including both p53+/+ and p53-mutant cancer cell lines.
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