usp7 in 8

Benzamide, 4-[6-amino-4-ethyl-5-(4-hydroxyphenyl)-3-pyridinyl]-N-methyl- is a selective ubiquitin-specific protease 7 (USP7) inhibitor with an IC50 of 1.4 μM. USP7-IN-8 (GNE-6776) has anticancer effects.

USP7-IN-18 (Compound X21) serves as a novel USP7 inhibitor by directly suppressing enzyme activity and modulating downstream pathways, including the newly identified PCLAF target. At concentrations of 0.25-1 μM for 24 hours, it exhibits inhibitory effects. USP7-IN-18 effectively reduces proliferation in leukemia (RS4;11) and colon cancer (MC38/CT26.WT) cells at 0.01-100 μM over 72 hours. It demonstrates high selectivity for USP7 at 2.5 μM within 0.5 hours, surpassing eight other deubiquitinating enzymes. SPR analysis shows that at 1.95-2000 nM for 3 minutes, the compound binds the catalytic domain of USP7 with a KD value of 4.9 μM.