XL177A is a potent, selective and irreversible inhibitor of Ubiquitin specific peptidase 7 (USP7) with IC50 of 0.34?nM.
Evaluation of the cellular effects of XL177A reveals that selective USP7 inhibition suppresses cancer cell growth predominantly through a p53-dependent mechanism: XL177A specifically upregulates p53 transcriptional targets transcriptome-wide, hotspot mutations in TP53 but not any other genes predict response to XL177A across a panel of ~500 cancer cell lines, and TP53 knockout rescues XL177A-mediated growth suppression of TP53 wild-type (WT) cells.[1]
[1] Nathan J Schauer, et al. Sci Rep. 2020 Mar 24;10(1):5324.