Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer with marginal life expectancy even with the most aggressive available therapy. We have identified a previously unanticipated vulnerability of glioblastoma cells which when targeted, leads to rapid cell death of tumor cells isolated from patients diagnosed with GBM. The cellular mechanism has been identified and involves an increased vulnerability of GSCs to massive vacuolization which can be induced by a small molecule, termed Vacquinol-1. The vacuolization results from an induction of massive macropinocytosis leading to cytoplasmic membrane rupture and cell death. In this project we have: 1) Compared potency and efficacy with competing compounds in development stage. 2) Established the optimal dosage regimen based on in vitro and in vivo cytotoxicity and brain exposure measurements. 3) Developed a GMP-compatible stereo-selective synthesis of an appropriate Vacquinol-1 isomer. 4) We have together with Karolinska Institutet Innovations AB protected the intellectual property, validated commercialization potential, establish a development plan and attracted venture capital for development of the discovery.
