BAI1 (Bax channel blocker)

Alias: BAI1; BAI 1; BAI-1; Brain-specific angiogenesis inhibitor 1
Cat No.:V5240 Purity: ≥98%
BAI1 is a novel, potent and direct allosteric inhibitor of BAX with a dissociation constant (Kd) of 15.0 ± 4 μM.
BAI1 (Bax channel blocker) Chemical Structure CAS No.: 335165-68-9
Product category: Bcl-2
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description
BAI1 is a novel, potent and direct allosteric inhibitor of BAX with a dissociation constant (Kd) of 15.0 ± 4 μM. In both healthy and unhealthy contexts, BAX plays a crucial role in the mitochondrial cell death pathway's response to a variety of stimuli. Cytosolic BAX is activated and translocated in a conformational manner upon binding by BH3-only proteins, which causes the permeabilization of the mitochondrial outer membrane. Despite the obvious therapeutic potential of preventing BAX-mediated cell death in a variety of diseases, efforts to rationally target BAX and develop inhibitors have proven difficult. BAX activation conformational events that prevent mitochondrial translocation and oligomerization are inhibited by BAIs. Our findings point to a novel paradigm for the efficient and targeted pharmacological targeting of BAX to support the rational design of BAX-mediated cell death inhibitors.
Biological Activity I Assay Protocols (From Reference)
Targets
Bax (Kd = 15.0 μM)
ln Vitro
BAX activation inhibitor 1 (BAI1) demonstrates inhibition of tBID-induced BAX-mediated membrane permeabilization in a dose dependent manner with an IC50 of 3.3 μM. At an original allosteric site, BAI1 binds to monomeric BAX. While BAI1 does not directly compete with the activator to inhibit conformational activation and oligomerization of BAX in solution, it does so through an allosteric mechanism that favors the inactive BAX. Additionally, BAI1 inhibited BAX membrane association and translocation brought about by tBID (IC50 = 5 ± 1 μΜ) or BIM SAHB (IC50 = 2 ± 1 μΜ) in a dose-dependent manner and with an IC50 that was comparable to BAX-mediated liposomal release. Only BAX-dependent cell death is inhibited by BAI1[1].
Cell Assay
Caspase 3/7 assay of WT MEFs after pro-apoptotic TNF/CHX treatment, whether BAI1 was given in conjunction with it or not at the recommended doses for 8 hours.
References

[1]. Nat Chem Biol . 2019 Apr;15(4):322-330.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C19H21BR2N3O
Molecular Weight
540.11942
Exact Mass
465.0051
Elemental Analysis
C, 48.85; H, 4.53; Br, 34.21; N, 8.99; O, 3.42
CAS #
335165-68-9
Related CAS #
335165-68-9
Appearance
Solid powder
SMILES
C1CN(CCN1)CC(CN2C3=C(C=C(C=C3)Br)C4=C2C=CC(=C4)Br)O
InChi Key
KUUJEXLRLIPQQJ-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H21Br2N3O/c20-13-1-3-18-16(9-13)17-10-14(21)2-4-19(17)24(18)12-15(25)11-23-7-5-22-6-8-23/h1-4,9-10,15,22,25H,5-8,11-12H2
Chemical Name
1-(3,6-dibromocarbazol-9-yl)-3-piperazin-1-ylpropan-2-ol
Synonyms
BAI1; BAI 1; BAI-1; Brain-specific angiogenesis inhibitor 1
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~18 mg/mL (~38.5 mM)
Ethanol: ~3 mg/mL (~6.4 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 1.87 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 18.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 1.87 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 18.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.8514 mL 9.2572 mL 18.5144 mL
5 mM 0.3703 mL 1.8514 mL 3.7029 mL
10 mM 0.1851 mL 0.9257 mL 1.8514 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.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • BAI1 binds to monomeric BAX at a novel allosteric site. Nat Chem Biol . 2019 Apr;15(4):322-330.
  • BAI1 allosterically inhibits BIM BH3-mediated BAX activation and oligomerization. Nat Chem Biol . 2019 Apr;15(4):322-330.
  • Structural and biochemical mechanism of BAI1-mediated BAX inhibition. Nat Chem Biol . 2019 Apr;15(4):322-330.
  • BAI1 inhibits cell death in BAX-dependent manner. Nat Chem Biol . 2019 Apr;15(4):322-330.
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