GNE6776 是一种具有口服活性的选择性USP7抑制剂。

GNE-6776 is a selective USP7 inhibitor.

GNE-6776 non-covalently targets USP7 12?? 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.

Although efficacious exposure is only transiently achieved, GNE-6776 causes modest, although significant, EOL-1 xenograft growth delay.

2009273-71-4

C20H20N4O2

348.406

GEN6776

DMSO:310 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years