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Purity: ≥98%
BTSA1 (BTSA-1) is a novel and potent BAX (BCL2-associated X protein) activator with antitumor activity. By specifically and strongly binding to the N-terminal activation site of BAX and causing conformational changes there, it triggers BAX-mediated apoptosis. While sparing healthy cells, BTSA1-induced BAX activation efficiently promotes apoptosis in leukemia cell lines and patient samples. BAX expression amounts and cytosolic conformation control BTSA1 sensitivity. BTSA1 increased host survival without causing any toxicity while effectively suppressing human acute myeloid leukemia (AML) xenografts. The BCL-2 family protein BAX is a central mediator of apoptosis. By inhibiting BAX and its activators, anti-apoptotic BCL-2 protein overexpression aids in the development of tumors and therapy resistance.
| Targets |
Bax (IC50 = 250 nM); Bax (IC50 = 144 nM)
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| ln Vitro |
BTSA1 has no capacity to directly activate the pro-apoptotic homolog BAK. Recombinant soluble BAX is potently and dose-responsively translocated to the mitochondrial membrane by treatment with BTSA1, which is followed by the induction of BAX oligomerization. Cancer cells are more likely to undergo apoptosis when BAX is activated by BTSA1. With IC50 values ranging between 1 and 4 μM, BTSA1 decreases the viability of all AML cell lines in a dose-dependent manner, with a complete effect occurring within 24 hours of treatment. All five AML cell lines exhibit dose-dependent caspase-3/7 activation[1].
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| ln Vivo |
BTSA1 potently suppresses human acute myeloid leukemia (AML) xenografts and increases host survival without toxicity. The healthy stem cellenriched (LSK) cells, common myeloid progenitors, granulocyte-monocyte progenitors, and megakaryocyte-erythrocyte progenitors are well-tolerated in mice and exhibit no toxic effects. A 10 mg/kg dose of BTSA1 reaches sufficient levels (~15 μM) to cause BAX activation and apoptosis in leukemia cells while also having a significant half-life in mouse plasma (T1/2 = 15 hr) and oral bioavailability (%F = 51). As a result, BTSA1 has excellent pharmacokinetics, is orally bioavailable, significantly inhibits tumor growth in leukemia xenografts by inducing apoptosis, and at therapeutically effective doses exhibits no detectable toxicity in the hematopoietic system or other tissues[1].
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| Cell Assay |
AML cells (seeded at 2 × 104 cells/well) are incubated with serial dilutions of BTSA1 or BTSA2 or vehicle (0.15% DMSO) in no FBS media for 2.5 hours before 10% FBS replacement is added to a final volume of 100 l. At 24 hours, cell viability is assessed.
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| References |
| Molecular Formula |
C21H14N6OS2
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| Molecular Weight |
430.51
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| Exact Mass |
430.0671
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| Elemental Analysis |
C, 58.59; H, 3.28; N, 19.52; O, 3.72; S, 14.89
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| CAS # |
314761-14-3
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| Appearance |
Solid powder
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| SMILES |
C1=CC=C(C=C1)C2=CSC(=N2)N3C(=O)C(=C(N3)C4=CC=CC=C4)N=NC5=NC=CS5
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| InChi Key |
CTRCXGFSYFTJIW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H14N6OS2/c28-19-18(24-25-20-22-11-12-29-20)17(15-9-5-2-6-10-15)26-27(19)21-23-16(13-30-21)14-7-3-1-4-8-14/h1-13,26H
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| Chemical Name |
5-phenyl-2-(4-phenyl-1,3-thiazol-2-yl)-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-3-one
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3228 mL | 11.6141 mL | 23.2283 mL | |
| 5 mM | 0.4646 mL | 2.3228 mL | 4.6457 mL | |
| 10 mM | 0.2323 mL | 1.1614 mL | 2.3228 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Cancer Cell.2017 Oct 9;32(4):490-505.e10. |
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BTSA1 Is a High-Affinity and Selective BAX Trigger Site Activator.Cancer Cell.2017 Oct 9;32(4):490-505.e10. |
BTSA1 Induces All Steps of the BAX Activation Pathway.Cancer Cell.2017 Oct 9;32(4):490-505.e10. |
BTSA1 Induces Robust and Rapid BAX-Mediated Apoptosis.Cancer Cell.2017 Oct 9;32(4):490-505.e10. |
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Specificity of BTSA1 for Cellular BAX, Cytosolic BAX Monomer, and the BAX Trigger Site.Cancer Cell.2017 Oct 9;32(4):490-505.e10. |
BTSA1 Is Effective against Patient AML Blasts and Pre-leukemic Stem Cells without Affecting Normal Hematopoietic Progenitor Cells and Demonstrates Significant Synergy with Venetoclax.Cancer Cell.2017 Oct 9;32(4):490-505.e10. |
BTSA1 Demonstrates Potent Efficacy in Killing Human AML In Vivo.Cancer Cell.2017 Oct 9;32(4):490-505.e10. |
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BTSA1 Is Well Tolerated without Toxicity to Normal Cells In Vivo.Cancer Cell.2017 Oct 9;32(4):490-505.e10. |
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