USP28-IN-4 is a USP28 inhibitor (IC50=0.04 μM) with high selectivity over USP2, USP7, USP8, USP9x, UCHL3 and UCHL5. USP28-IN-4 shows cytotoxicity against cancer cells, down-regulates the cellular level of c-Myc through ubiquitin-proteasome system. USP28-IN-4 also decreases the ankyrase-1/2 level in vitro. USP28-IN-4 enhance the sensitivity of colorectal cancer cells to Regorafenib .
USP28-IN-4 (compound 9p) (12.5 μM, 15 μM; 3 d) inhibits colony formation of human colorectal cancer cells HCT116 (15 μM) and Ls174T (12.5 μM)[1].USP28-IN-4 (20-80 μM; 24 h) down-regulates the level of c-Myc by enhancing its degradation via ubiquitin-proteasome system (UPS)[1].
References:
[1]. Zhou D, et al. Structure-based discovery of potent USP28 inhibitors derived from Vismodegib. Eur J Med Chem. 2023 Jun 5;254:115369.