HA15 is a potent and specific inhibitor of ER chaperone BiP/GRP78/HSPA5, inhibits the ATPase activity of BiP, with anti-cancerous activity^[1]. IC50 & Target: BiP/GRP78/HSPA5^[1] In Vitro: HA15 (10 μM; 1-24 hours) induces an early endoplasmic reticulum stress (ER Stress)^[1].
HA15 (0-10μM; 24 hours) decreases melanoma cell viability in a dose-dependent manner compared with control conditions (DMSO), with an IC₅₀ of 1-2.5 μM in A375 cells^[1].
HA15 (1-10 μM; 24 hours) induces apoptosis in A375 cells^[1].
HA15 (1-24 μM; 24 hours) induces autophagy^[1].
HA15 (10 μM; 48 hours) has high efficiency in inducing cell death and ER stress in BRAF-inhibitor-resistant melanoma cells. And HA15 inhibits tumor growth through autophagic and apoptotic mechanisms initiated by ER stress^[1].
No deleterious effects on the viability of normal human melanocytes or human fibroblasts were observed with low or high doses of HA15^[1].
In Vivo: HA15 (0.7 mg/mouse/day; i.h.; over 2 weeks) inhibits melanoma tumor development in mice, induces no apparent toxicity and no change in their behavior, body mass, or liver mass, suggesting an absence of hepatomegaly^[1].