BTSA1, a pharmacologically optimized 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-induced BAX activation effectively promotes apoptosis in leukemia cell lines and patient samples while sparing healthy cells. BAX expression levels and cytosolic conformation regulate sensitivity to BTSA1. BTSA1 potently suppressed human acute myeloid leukemia xenografts and increased host survival without toxicity[1]. BTSA1, or Bax overexpression successfully abolished the inhibitory effect of L-cystathionine on Hcy-induced MPTP opening, caspase-9 and caspase-3 activation, and HUVEC apoptosis[2].
BTSA1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Solid tumor cell lines (e.g., pancreatic cancer BxPC-3 and colon cancer SW480)
10 μM
4 hours
Evaluate the ability of BTSA1.2 to induce BAX activation and translocation
Nat Commun. 2022 Mar 7;13(1):1199.
OCI-AML3 cells
5 μM
6, 12, and 24 hours
To assess the effect of BTSA1 on OCI-AML3 cell viability at different time points, results showed that BTSA1 significantly reduced cell viability within 6 hours
Cancer Cell. 2017 Oct 9;32(4):490-505.e10.
Human AML cell lines
1–4 μM
24 hours
To evaluate the ability of BTSA1 to induce apoptosis in AML cell lines, results showed that BTSA1 significantly reduced cell viability and induced apoptosis
Cancer Cell. 2017 Oct 9;32(4):490-505.e10.
Human umbilical vein endothelial cells (HUVECs)
0.625 μmol/L
2.5 hours
BTSA1, a Bax agonist, promotes Bax translocation to mitochondria without affecting its expression. In HUVECs, pretreatment with BTSA1 successfully abolished the inhibitory effect of L-cystathionine on Hcy-induced MPTP opening, caspase-9 and caspase-3 activation, and HUVEC apoptosis.
Oxid Med Cell Longev. 2019 Nov 25;2019:1253289.
BTSA1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
SW480 colon cancer xenograft model
Oral gavage
200 mg/kg
Once daily for 7 days
Evaluate the efficacy of BTSA1.2 and Navitoclax combination therapy in colon cancer xenograft models
Nat Commun. 2022 Mar 7;13(1):1199.
NOD-SCID IL2Rγ null (NSG) mice
Human AML xenograft model
Intraperitoneal injection
10 mg/kg
Every 48 hours for 3 weeks
To evaluate the anti-tumor activity and safety of BTSA1 in AML xenograft models, results showed that BTSA1 significantly suppressed leukemia growth and increased host survival without detectable toxicity
Cancer Cell. 2017 Oct 9;32(4):490-505.e10.
C57BL/6 mice
Bleomycin-induced pulmonary fibrosis model
Intraperitoneal injection
10 mg/kg
Once every 2 days
Evaluate the therapeutic effect of BTSA1 on pulmonary fibrosis, results showed BTSA1 significantly reduced the number of senescent myofibroblasts in lung tissue and alleviated both reversible and irreversible pulmonary fibrosis
搜索
