Napabucasin is an inhibitor of cancer cell stemness. It reduces growth in a panel of cancer cells enriched for high stemness (IC50s = 0.291-1.249 μM) and decreases protein and gene expression of various self-renewal and pro-survival markers including Nanog, Smo, Axl, Atm, and Bmi-1 in a concentration-dependent manner in FaDu head and neck squamous cell carcinoma (HNSCC) cells. In vivo, napabucasin (20 mg/kg per day) inhibits tumor growth in a PaCa-2 mouse xenograft model and prevents tumor regrowth after cessation of treatment. It blocks formation of spleen and liver metastases in an HT29 intrasplenic nude mouse model system (ISMS) model. Napabucasin (40 mg/kg, i.p.) also reduces tumor volume in PC3 and 22RV1 prostate cancer mouse xenograft models.
