BAU-243 (BAU243) is a novel BH3 mimetic Bcl-2 inhibitor with a high affinity, effectively reduces overall GBM cell proliferation including a subpopulation of cancer-initiating cells.
BAU-243 reduces survival of GBM cells and tumor-initiating stem cells (A172 cells, IC50=18.2 uM).
BAU-243 induces limited apoptosis and cell cycle arrest in low Bcl-2 expressing cells.
BAU-243 does not induce apoptosis in high Bcl-2 expressing SHSY-5Y cells despite the significant anti-proliferative effect.
BAU-243 promotes autophagic cell death through the disruption of Beclin 1 and Bcl-2 interaction, regardless of Bcl-2 expression level.
BAU-243 (25 mg/kg) reduced tumor growth in vivo with lower dose compared to other BH3 mimetics (ABT-263, 75 mg/kg).
BAU-243 demonstrated a remarkable anti-proliferative effect on the cancer sub-population that is considered a true representative of tumor-initiating GBM stem-like cells.
BAU-243 interacts with critical residues of Bcl-2 that plays role in the binding of Beclin 1 BH3 domain, showing that it can hinder Beclin 1:Bcl-2 complex formation, freeing Beclin 1 to activate the autophagy pathway.