BTSA1 是一种有口服活性的BAX激活剂,IC50为 250 nM,EC50为 144 nM。它以高亲和力和特异性与 N 末端激活位点结合,并诱导BAX发生构象变化,从而导致BAX介导的细胞凋亡。
产品描述
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.
体外活性
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].
体内活性
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].
Cas No.
314761-14-3
分子式
C21H14N6OS2
分子量
430.51
储存和溶解度
DMSO:65 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years