5428-80-8

Vacquinols are a new class of quinine-derivatives that stimulate death in glioblastoma cells by massive macropinocytotic vacuolization, ATP depletion, and cytoplasmic membrane rupture. A key effector of vacquinols is MAPK kinase 4 (MKK4). Vacquinol-1 is an activator of MKK4-dependent macropinocytotic cell death in glioblastoma cells. It induces ATP depletion in glioblastoma cells (IC₅₀ = 3.14 μM at 1 day) without affecting fibroblasts, embryonic stem cells, or osteosarcoma cells. Vacquinol-1 is orally bioavailable with good brain penetrance and excellent pharmacokinetics. Oral administration of vacquinol-1 (20 mg/kg once daily for five days) substantially impairs the growth of engrafted glioblastoma cell tumors in mice and prolongs survival.

Vacquinol-1 is in the vacquinol class of quinine derivatives that stimulate death in glioblastoma cells through massive macropinocytotic vacuolization, ATP depletion and eventual cytoplasmic membrane rupture.