DUB-IN-2

DUB-IN-2 is an inhibitor of ubiquitin-specific protease 8 (USP8; IC₅₀ = 280 nM).¹ It is selective for USP8 over USP7 (IC₅₀ = >100 µM). DUB-IN-2 increases the level of programmed cell death protein ligand 1 (PD-L1) in H460 cells when used at a concentration of 2 µM and PC-9 cells at 2 and 4 µM.² Intraperitoneal injection of DUB-IN-2 (1 mg/kg every other day), in combination with an anti-PD-L1 antibody and paclitaxel (Item No. 10461), decreases tumor weight, tumor size, and lung metastasis and increases CD8⁺ T cell numbers within the primary tumor in a 4T1 murine mammary carcinoma model.³

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1. Colombo, M., Vallese, S., Peretto, I., et al. Synthesis and biological evaluation of 9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile analogues as potential inhibitors of deubiquitinating enzymes. ChemMedChem 5(4), 552-558 (2010).

2. Xiong, W., Gao, X., Zhang, T., et al. USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy. Nat. Commun. 13(1), 1700 (2022).

3. Xie, F., Zhou, X., Li, H., et al. USP8 promotes cancer progression and extracellular vesicle-mediated CD8⁺ T cell exhaustion by deubiquitinating the TGF-β receptor TβRII. EMBO J. 41(16), e108791 (2022).