[CAS NO. 1247819-59-5]  P22077

P22077 is an analog of the recently discovered USP7 inhibitor P5091. P22077 has negligible activity versus DEN1 and SENP2core over the concentration range tested, but inhibits USP7 with an IC50 of 8 μM. The inhibitory activities of P22077 in vitro against a panel of DUBs, cysteine proteases, and other families of proteolytic enzymes demonstrate that P22077 inhibits USP7 and the closely related DUB USP47. P22077 inhibits a smaller subset of DUBs at a concentration of 15–45 mM in cell lysates. P22077 induces (tumor) cell death with EC50 values in the low micromolar range. P22077 inhibition exhibited changes in ubiquitylated protein levels that are distinct from the broad specificity inhibitor. P22077 treatment of U2OS cells during release from G1/S arrest induces with hydroxyurea resulted in a dose-dependent loss of claspin protein and a concomitant decrease in phospho Serine 317 Chk1. Furthermore, quantitative MS suggestes the E3 ubiquitin ligase components RBX1, DCAF7, DCAF11, and the DNA damage binding protein 1 (DDB1) to be reduced upon cellular treatment with P22077.