9H-Indeno[1,2-b]pyrazine-2,3-dicarbonitrile, 9-[(2-propen-1-yloxy)imino]-

DUB-IN-3 is an inhibitor of ubiquitin-specific protease 8 (USP8; IC50 = 0.56 µM).1 It is selective for USP8 over USP7 (IC50 = >100 µM). DUB-IN-3 is also an inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) papain-like protease (PLpro) when Z-LRGG-AMC is used as a substrate (IC50 = 12.5 µM) but not when the larger substrate Ub-AMC is used (IC50 = >10 µM).2 It reduces glutathione (GSH) levels and cystine uptake, as well as increases ferrous iron and reactive oxygen species (ROS) levels, in HCCLM3 cells when used at concentrations of 0.2 or 0.5 µM.3 It decreases the viability of HCCLM3 cells when used in combination with the ferroptosis inducer RSL3 (Item No. 19288), an effect that can be blocked by the ferroptosis inhibitor ferrostatin-1 (Item No. 17729). DUB-IN-3 (0.1 and 0.2 µM) reduces the proliferation, migration, and oncosphere formation ability of HCCLM3 and Hep3B hepatocellular carcinoma cells. It also reduces tumor growth and metastasis in HCCLM3 and Hep3B mouse models of metastatic lung cancer when administered at a dose of 5 mg/kg per day.WARNING This product is not for human or veterinary use.