BTSA1 | CAS#314761-14-3 | Bcl-2 modulator

MedKoo Cat#: 584440 | Name: BTSA1

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

BTSA1 is 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. It effectively promotes apoptosis in leukemia cell lines and patient samples while sparing healthy cells.

Chemical Structure

BTSA1

CAS#314761-14-3

Theoretical Analysis

MedKoo Cat#: 584440

Name: BTSA1

CAS#: 314761-14-3

Chemical Formula: C21H14N6OS2

Exact Mass: 430.0671

Molecular Weight: 430.50

Elemental Analysis: C, 58.59; H, 3.28; N, 19.52; O, 3.72; S, 14.89

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,950.00	Ready to ship

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Related CAS #

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Synonym

BTSA1; BTSA-1; BTSA 1; ANA-38; ANA 38; ANA38;

IUPAC/Chemical Name

1H-Pyrazole-4,5-dione, 3-phenyl-1-(4-phenyl-2-thiazolyl)-, 4-[2-(2-thiazolyl)hydrazone]

InChi Key

KYVZVVOQWWCVPP-HKOYGPOVSA-N

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/h1-13H,(H,22,25)/b24-18+

SMILES Code

O=C(N(C1=NC(C2=CC=CC=C2)=CS1)N=C/3C4=CC=CC=C4)C3=N\NC5=NC=CS5

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A21T01K26

QC Data

View QC data: current batch, Lot#A21T01K26

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

BTSA1 is a potent BAX activator with an IC50 of 250 nM and an EC50 of 144 nM.

In vitro activity:

The ability of BTSA1 to induce apoptosis was evaluated in human AML cell lines that have p53 and/or NRAS mutations and a range of expression levels for BAX and anti-apoptotic BCL-2 proteins. BTSA1 reduced viability of all AML cell lines in a dose-dependent manner with half maximal inhibitory concentration (IC50) values ranged between 1–4 μM that leads to complete effect within 24 hr treatment (Figure 3A). Cellular viability measured for select cell lines at different time points displayed substantial cell death activity by BTSA1 within 6 hr of treatment (Figure 3B). The substantial and rapid loss of viability of leukemia cells is consistent with the biochemical effects that characterize BAX activation and apoptosis, which was observed promptly after BTSA1 treatment. Significant BAX mitochondrial translocation was induced in a BTSA1 dose-dependent manner (Figure 3C). BTSA1-induced BAX translocation coincided with the release of cytochrome c from the mitochondria to the cytosol (Figure 3C). BTSA1 induced dose-dependent caspase-3/7 activation in all five AML cell lines (Figure 3D). Moreover, loss of viability, apoptosis induction and cytotoxicity occurred at the same effective dose of BTSA1 (Figure S3A, S3B). A more direct consequence of the BTSA1 activity is considered to be the loss of mitochondrial membrane potential that can be caused by BAX mitochondrial translocation. Interestingly,a linear correlation with BAX protein levels and the degree of mitochondrial membrane potential loss induced by BTSA1 was found, suggesting that mitochondrial damage induced by BTSA1 is proportional to BAX levels in leukemia cells (Figure 3H). Taken together, BTSA1 induces robust apoptosis in leukemia cells through rapid BAX activation. BTSA1’s activity directly correlates with increasing BAX protein levels, which can overcome blockade of the endogenous anti-apoptotic BCL-2 proteins. Reference: Cancer Cell. 2017 Oct 9; 32(4): 490–505.e10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793879/

In vivo activity:

The in vivo activity and safety of BTSA1-induced BAX activation was next evaluated in human AML xenografts and in healthy cells and tissues. Human leukemia THP-1 xenografts were generated in mice and after engraftment at 10 days, mice were randomly divided into two groups and treated with either vehicle or 10 mg/kg BTSA1 every 48 hr (Figure 6A). Mice treated with BTSA1 had significantly increased survival when compared to vehicle-treated mice (median survival 40 days in control vs 55 days in BTSA1treated) and 43% of BTSA1-treated mice were alive at day 60 and had no signs of AML infiltrates (Figure 6B). To confirm antileukemic efficacy of BTSA1, the experiment was repeated and after 3 weeks of BTSA1 treatment, AML tumor burden from bone marrow and liver was evaluated by flow cytometry using anti-hCD45 and anti-hCD15 antibodies (Figure 6C). Human leukemia infiltration was detected in livers of vehicle treated mice while BTSA1 treatment induced significant suppression of leukemia growth (Figure 6D–6F). Reference: Cancer Cell. 2017 Oct 9; 32(4): 490–505.e10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793879/

	Solvent	mg/mL	mM
Solubility
	DMSO	53.0	123.11

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 430.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wang X, Wang Y, Zhang L, Zhang D, Bai L, Kong W, Huang Y, Tang C, Du J, Jin H. L-Cystathionine Protects against Homocysteine-Induced Mitochondria-Dependent Apoptosis of Vascular Endothelial Cells. Oxid Med Cell Longev. 2019 Nov 25;2019:1253289. doi: 10.1155/2019/1253289. PMID: 31885769; PMCID: PMC6899331. 2. Reyna DE, Garner TP, Lopez A, Kopp F, Choudhary GS, Sridharan A, Narayanagari SR, Mitchell K, Dong B, Bartholdy BA, Walensky LD, Verma A, Steidl U, Gavathiotis E. Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia. Cancer Cell. 2017 Oct 9;32(4):490-505.e10. doi: 10.1016/j.ccell.2017.09.001. PMID: 29017059; PMCID: PMC5793879.

In vitro protocol:

In vivo protocol:

1. Reyna DE, Garner TP, Lopez A, Kopp F, Choudhary GS, Sridharan A, Narayanagari SR, Mitchell K, Dong B, Bartholdy BA, Walensky LD, Verma A, Steidl U, Gavathiotis E. Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia. Cancer Cell. 2017 Oct 9;32(4):490-505.e10. doi: 10.1016/j.ccell.2017.09.001. PMID: 29017059; PMCID: PMC5793879.

[1] Reyna DE, et al. Cancer Cell. 2017, 32(4):490-505.