BTSA1

BTSA1 is a potent, high affinity and orally active BAX activator with an IC50 of 250 nM and an EC50 of 144 nM. BTSA1 binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis[1].

Signaling Pathways >> Apoptosis >> Bcl-2 Family

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Bax:250 nM (IC50)

Bax:144 nM (EC50)

BTSA1 (5 μM; 6-24 hours; human AML cell lines) treatment reduced viability of all AML cell lines and displays substantial cell death activity within 6 hours[1]. BTSA1 (2.5-10 μM; 6 hours; NB4 cells) treatment induces BAX translocation coincided with the release of cytochrome c from the mitochondria to the cytosol. Significant BAX mitochondrial translocation is induced in a BTSA1 dose-dependent manner[1]. BTSA1 (0.15625-10 μM; 4-24 hours; OCI-AML3 cells) treatment induces dose-dependent caspase-3/7 activation in OCI-AML3 cells. Caspase-3/7 activation is monitored within 4-24 hours and maximal caspase-3/7 activation is detected in 4 hours[1]. Cell Viability Assaysup>[1] Cell Line: Human AML cell lines< Concentration: 5 μM Incubation Time: 6 hours, 12 hours, 24 hours Result: Reduced viability of all AML cell lines. Displayed substantial cell death activity within 6 hours. Western Blot Analysis[1] Cell Line: NB4 cells Concentration: 2.5 μM, 5 μM, 10 μM Incubation Time: 6 hours Result: Significant BAX mitochondrial translocation was induced in a dose-dependent manner. Apoptosis Analysis[1] Cell Line: OCI-AML3 cells Concentration: 0.15625 μM, 0.3125 μM, 0.625 μM, 1.25 μM, 2.5 μM, 5 μM, 10 μM Incubation Time: 4 hours, 6 hours, 8 hours, 12 hours, 24 hours Result: Induced dose-dependent caspase-3/7 activation in OCI-AML3 cells. Caspase-3/7 activation was monitored within 4-24 hr and maximal caspase-3/7 activation was detected in 4 hr.

BTSA1 (10 mg/kg; intraperitoneal injection; every two days; NOD-SCID IL2Rγ null (NSG) mice) treatment significantly increases survival when compared to vehicle-treated mice. BTSA1 treatment induces significant suppression of leukemia growth[1]. Animal Model: NOD-SCID IL2Rγ null (NSG) mice (6-8 weeks old) with THP-1 cells[1] Dosage: 10 mg/kg Administration: Intraperitoneal injection; every two days Result: Significantly increased survival when compared to vehicle-treated mice.

[1]. Reyna DE, et al. Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia. Cancer Cell. 2017 Oct 9;32(4):490-505.e10.