gne-6640

Description: GNE-6640, an analog of GNE-6776, is a novel potent and selective inhibitor of USP7 (ubiquitin-specific protease-7). It induces tumour cell death and enhances cytotoxicity with chemotherapeutic agents and targeted compounds, including PIM kinase inhibitors. Structural studies reveal that GNE-6640 non-covalently targets USP7 12?Å distant from the catalytic cysteine. GNE-6640 attenuates ubiquitin binding and thus inhibits USP7 deubiquitinase activity. GNE-6640 interacts with acidic residues that mediate hydrogen-bond interactions with the ubiquitin Lys48 side chain, suggesting that USP7 preferentially interacts with and cleaves ubiquitin moieties that have free Lys48 side chains. Deubiquitinase enzymes cleave ubiquitin from substrates and are implicated in disease; for example, ubiquitin-specific protease-7 (USP7) regulates stability of the p53 tumour suppressor and other proteins critical for tumour cell survival.

References: Nature. 2017 Oct 26; 550(7677):534-538.

Related CAS#:2009273-60-1 (GNE-6776)