3-Acridinecarboxamide, 9-chloro-5,6,7,8-tetrahydro-N-[(4S)-5-[4-hydroxy-4-[[7-[[3-(4-methyl-1-piperazinyl)-1-oxopropyl]amino]-4-oxo-3(4H)-quinazolinyl]methyl]-1-piperidinyl]-5-oxo-4-(phenylmethyl)pentyl]-

Biological Activity

XL177A is a highly potent and selective irreversible USP7 inhibitor with an IC50 of 0.34 nM. XL177A elicits cancer cell killing through a p53-dependent mechanism[1]. XL177A is a potent USP7 inhibitor and p53 stabilizer in cyto. XL177A suppresses cancer cell growth predominantly through a p53-dependent mechanism. XL177A labels the catalytic cysteine, C223, of USP7 with exquisite selectivity for USP7 across the DUBome and human proteome[1]. XL177A (1 μM) induces complete G1 arrest in MCF7 cells after 24 hours[1].Treatment of MCF7 cells, which express WT TP53, with XL177A (0.001- 10 μM) induces rapid degradation of HDM2 within 2 hours, followed by increases in p53 and downstream p21 protein levels[1].

References

[1]. Nathan J Schauer, et al. Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism. Sci Rep.2020 Mar 24;10(1):5324.