tcsc0031103 GNE-6776

GNE-6776 is a selective USP7 inhibitor.

IC50 & Target: USP7^[1]

In Vitro: GNE-6776 non-covalently targets USP7 12 Å distant from the catalytic cysteine. GNE-6776 attenuates ubiquitin binding and thus inhibits USP7 deubiquitinase activity. GNE-6776 interacts with acidic residues that mediate hydrogen-bond interactions with the ubiquitin Lys48 side chain. GNE-6776 targets cellular USP7, MDM2, and p53 signalling pathways.GNE-6776 selectively inhibits recombinant USP7 relative to 36 other deubiquitinases. GNE-6776 remains selective even at 100 μM, a more than sixfold higher concentration than used in cellular assays. GNE-6776 significantly inhibits USP7 while remaining selective against 44-47 other detected deubiquitinases^[1].

In Vivo: Although efficacious exposure is only transiently achieved, GNE-6776 causes modest, although significant, EOL-1 xenograft growth delay^[1].