GNE-6640 is an inhibitor of ubiquitin-specific protease 7 (USP7; IC50 = 0.75 ?M).1 It is selective for USP7 over USP47 and USP5 (IC50s = 20.3 and >200 ?M, respectively). GNE-6640 enhances ubiquitination of the USP7 substrate MDM2 in HCT116 colon cancer cells (IC50 = 0.23 ?M) and reduces cell viability in a panel of 108 cell lines (IC50s = <10 ?M for all). GNE-6640 (10-70 ?M) enhances apoptosis induced by doxorubicin or cisplatin in MCF-7 and U2OS cancer cells, respectively.
1.Kategaya, L., Di Lello, P., Rouge, L., et al.USP7 small-molecule inhibitors interfere with ubiquitin bindingNature550(7677)534-538(2017)