SJB2-043 analog is an inhibitor of OTUB1 and ubiquitin-specific protease 8 (USP8; IC50s = 0.17 and 0.28 nM, respectively) and a derivative of the USP1/UAF1 complex and SARS-CoV-2 PLPro inhibitor SJB2-043.1 It is selective for OTUB1 and USP8 over USP1, USP2, USP7, USP36, and ataxin-3 (IC50s = 1,370, 3,800, >10,000, 8,400, and >10,000 nM, respectively). SJB2-043 analog reduces viability in H1975, EBC-1, NCI H1703, H23, and A549 non-small cell lung cancer (NSCLC) cells (IC50s = 118, 172, 145, 431, and 1,004 nM, respectively). In vivo, SJB2-043 analog (5 mg/kg twice daily) decreases tumor volume in an H1975 mouse xenograft model.
References:
[1]. Tan, L., Shan, H., Han, C., et al.Discovery of potent OTUB1/USP8 dual inhibitors targeting proteostasis in non-small-cell lung cancerJ. Med. Chem.65(20)13645-13659(2022).