BTSA1 is a BAX activator that binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis.

BTSA1 has no capacity to directly activate the pro-apoptotic homolog BAK. BTSA1 treatment potently and dose-responsively induces membrane translocation of recombinant soluble BAX to the mitochondrial membrane, which is followed by induction of BAX oligomerization. BTSA1-induced BAX activation promotes apoptosis in cancer cells. BTSA1 reduces the viability of all AML cell lines in a dose-dependent manner with IC50 values ranged between 1 and 4 μM, which leads to complete effect within 24 hr treatment. It induces dose-dependent caspase-3/7 activation in all five AML cell lines[1].

BTSA1 potently suppresses human acute myeloid leukemia (AML) xenografts and increases host survival without toxicity. It is well-tolerated in mice with no toxic effects on healthy hematopoiesis, including healthy stem cell-enriched (LSK) cells, common myeloid progenitors, granulocyte-monocyte progenitors, and megakaryocyte-erythrocyte progenitors. BTSA1 has a substantial half-life in mouse plasma (T1/2 = 15 hr) and oral bioavailability (%F = 51), while a 10 mg/kg dose reaches sufficient levels (~15 μM) of BTSA1 to induce BAX activation and apoptosis in leukemia cells. Thus, BTSA1 is orally bioavailable with excellent pharmacokinetics, has significant anti-tumor activity in leukemia xenografts by promoting apoptosis, and at therapeutically effective doses it does not show any detectable toxicity in the hematopoietic system or other tissues[1].