NB-598

NB-598 is a potent and selective small molecule inhibitor of squalene epoxidase (SQLE), a rate-limiting enzyme in the cholesterol biosynthesis pathway that catalyzes the conversion of squalene to 2,3-epoxysqualene. Originally developed by Banyu Pharmaceutical as a cholesterol-lowering agent, NB-598 has emerged as a valuable research tool for investigating metabolic vulnerabilities in oncology. In high-grade serous ovarian cancer (HGSOC), NB-598 induces cytotoxicity not through cholesterol deprivation, but via the toxic accumulation of squalene, which triggers endoplasmic reticulum (ER) stress and activates apoptotic pathways involving JNK and p38 signaling. This mechanism highlights SQLE as a potential therapeutic target in cancers that are sensitive to squalene-induced lipotoxicity.