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Gallic acid inhibits USP2. 5 / 5
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"In contrast, our results indicate that GA could inhibit USP2 activity by covalently binding to the Cys284 residue, instead of the Cys276 residue within the catalytic site, of USP2."
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"In addition to the CETSA results, the drug affinity-responsive target stability assay showed that GA could prevent the pronase-mediated digestion of USP2 in a dose-dependent manner (Supporting Information Fig. S4)."
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"Specifically, we employed GA as a chemical probe and demonstrated that GA could covalently bind to and inhibit USP2 through an allosteric pocket."
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"As shown in Fig. 2I and J, GA inhibited the hydrolytic activity of USP2 against Ub-AMC in a concentration-dependent manner (Fig. 2I)."
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"We further revealed that the USP2 stabilizes KRAS by deubiquitination; consequently, USP2 inactivation induced by GA could lead to the destabilization of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo ."
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