In vitro activity: HA15 specifically targets chaperone BiP/GRP78/HSPA5. HA15 induces ER stress leading to cancer cell death by concomitant induction of autophagic and apoptotic mechanisms. HA15 also exhibited strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors. HA15 displayed anti-cancerous activity on all melanoma cells tested, including cells isolated from patients and cells that developed resistance to BRAF inhibitors. HA15 displayed activity against other liquid and solid tumors. HA15 also exhibited strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors.

Cell Assay: HA15 induces ER stress leading to cancer cell death. kills cancer cells by targeting BiP to increase ER stress, leading to melanoma cell death by concomitant induction of autophagic and apoptotic mechanisms. HA15 exhibits strong efficacy in melanoma cells. The 50% inhibitory concentration (IC50) in A375 cells was between 1 and 2.5 mM HA15.