Name: Bax channel blocker
Brand: Adooq Bioscience
SKU: A15335
Availability: InStock
Rating: 5 (1 reviews)

Biological Activity

Bioactivity / Mechanism

BAI1, the Bax channel blocker active moiety, directly binds inactive BAX. NMR mapping identified a pocket involving helices α3–α5, supporting an allosteric inhibitory mechanism; BAI1 also inhibited tBID-induced BAX permeabilization of liposomes. MST gave a reported Kd of 15.0 ± 4 μM. These findings concern the paper’s BAI1 material; they do not establish salt-specific potency equivalence or validate an Adooq lot. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target	Activity	Value
Bax

Cellular Effect

Cell Line	Activity	Value	Description	Reference
HeLa	IC50	0.52 μM	In vitro inhibition of Bax regulated release of cytochrome C was determined using liposome channel assay	[PMID: 14521400]

In Vitro Studies

In TNFα/cycloheximide-stimulated mouse embryonic fibroblasts, BAI1 reduced caspase-3/7 activation after 8 h (reported IC50 1.8 μM in wild-type cells). At 2 μM it suppressed the response in wild-type and Bak-deficient cells, with no significant suppression in Bax-deficient cells. The endpoint supports BAX dependence under these conditions. [1]

Victorelli et al. explicitly used Adooq A15335 BAI1 in irradiated MRC5 human fibroblasts. Treatment with 0.1–2.5 μM BAI1 over 10 days reduced secretion of the SASP factors IL-6, IL-8 and IP-10, with effects varying by concentration and cytokine; the 0.1 μM IL-8 comparison was not significant (P=0.06). These secretion endpoints do not demonstrate removal of senescent cells. [2]

Direct BAX binding and inhibition of liposomal permeabilization

Biochemical assay · Purified inactive human BAX; tBID-activated BAX in ANTS/DPX-loaded liposomes. [1]

BAI1 bound soluble BAX in ligand-observed NMR and MST assays. NMR perturbations localized an inhibitory pocket involving helices α3–α5; docking provided a proposed pose. BAI1 also inhibited tBID-induced BAX membrane permeabilization, supporting the authors’ allosteric-inhibition interpretation.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
BAI1 binding to inactive BAX	Kd 15.0 ± 4 μM	[1]
tBID-induced BAX-mediated ANTS release	Functional inhibition Dose-dependent inhibition over the tested 1.5–6 μM BAI1 series	[1]
Localization of BAI1 interaction with BAX	NMR mapping Perturbations cluster at a pocket formed by α3, α4, α5 and the α3–α4 loop	[1]

Literature-Reported Treatment Conditions

Treatment concentration: Liposome assay: BAI1 1.5–6 μM; BAX 400 nM; tBID 30 nM. Ligand-observed NMR: BAI1 150 μM and BAX 15 μM in Figure 1f. MST: BAI1 0.5–150 μM with labeled BAX 100 nM.
Exposure duration: Liposomes: 30 min BAX–BAI1 preincubation, followed by 30 min activation endpoint. MST: 10 min incubation.
Method: Cell-free NMR, MST and dye-release assays.
Vehicle: DMSO stocks diluted into assay buffer; NMR samples were DMSO matched.
Co-treatment: tBID activates BAX in the liposome assay.
Reported limits: Final DMSO percentage and experimental counterion are not specified in the reviewed main methods.

Methods and source locations

Compound reported in the paper: BAI1 (Bax channel blocker); Compound label in the paper: BAI1

Evidence concerns the paper’s BAI1 material. Salt-specific potency equivalence and performance of an Adooq lot were not tested.

Figure 1d–g; Figure 2; corresponding Results and Online Methods

BAI1 binding to inactive BAX: Microscale thermophoresis with 100 nM labeled BAX and increasing BAI1; 1:1 binding model. Figure 1g describes single points per titration, representative of 2 technical replicates and 3 independent experiments. The main text/caption does not define the ± term. — Results: Discovery of direct BAX activation inhibitors; Figure 1g; Online Methods: Microscale Thermophoresis

tBID-induced BAX-mediated ANTS release: 400 nM BAX, 30 nM tBID, read at 30 min; mean ± SD, n=3 replicates, representative of five independent experiments. Controls include BAX alone, compound without tBID, and BAX+tBID; Triton defines maximal release. No exact release percentages inferred from bars. — Figure 1d,e and caption; Online Methods: Liposomal permeabilization assay.

Localization of BAI1 interaction with BAX: 15N-BAX HSQC titration to BAX:BAI1 1:2, representative of three independent experiments; NMR-guided docking depicts a proposed binding pose, not a crystal structure. — Results: BAIs bind to inactive BAX at a novel allosteric site; Figure 2a–e and caption

BAX-dependent suppression of caspase-3/7 activation in MEFs

Cell-based study · Wild-type, Bax−/− and Bak−/− mouse embryonic fibroblasts stimulated with TNFα plus cycloheximide. [1]

BAI1 suppressed stimulus-induced caspase-3/7 activation in wild-type and Bak-deficient MEFs. It had no significant effect in Bax-deficient MEFs under the tested conditions. This supports BAX dependence in these models without establishing universal absence of BAK-related activity.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Inhibition of TNFα/cycloheximide-induced caspase-3/7 activation in wild-type MEFs	IC50 1.8 μM	[1]
Genotype dependence of BAI1 effect on stimulus-induced caspase-3/7 activation	Qualitative genotype comparison Suppression in wild-type and Bak−/− MEFs; no significant suppression in Bax−/− MEFs	[1]

Literature-Reported Treatment Conditions

Treatment concentration: BAI1 dose series 0.312–10 μM in Figure 5a; 2 μM for genotype comparisons in Figure 5b–d.
Exposure duration: 8 h co-treatment.
Method: Caspase-Glo 3/7 luminescence assay.
Vehicle: Compounds prepared in DMSO; final percentage not given in reviewed methods.
Co-treatment: TNFα 50 ng/mL plus cycloheximide (10 μg/mL in Figure 5a; a graded cycloheximide series in Figure 5b–d).
Reported limits: Final DMSO fraction not identified in reviewed main methods.

Methods and source locations

Compound reported in the paper: BAI1 (Bax channel blocker); Compound label in the paper: BAI1

Evidence concerns the paper’s BAI1 material. Salt-specific potency equivalence and performance of an Adooq lot were not tested.

Figure 5a–d; Results: BAI1 selectively inhibits BAX-dependent cell death; Online Methods: Caspase-3/7 activation and cell viability assays

Inhibition of TNFα/cycloheximide-induced caspase-3/7 activation in wild-type MEFs: Reported in Results; Caspase-Glo 3/7 endpoint at 8 h. Figure 5a uses TNFα 50 ng/mL and cycloheximide 10 μg/mL, with BAI1 titration. Mean ± SD; n=3 replicates, representative of three independent experiments. — Results: BAI1 selectively inhibits BAX-dependent cell death; Figure 5a and caption; Online Methods: Caspase-3/7 activation and cell viability assays

Genotype dependence of BAI1 effect on stimulus-induced caspase-3/7 activation: 2 μM BAI1 for 8 h with TNFα 50 ng/mL and graded cycloheximide. Untreated, BAI1-alone, and stimulus-alone controls shown. Figure 5a also includes single stimulus components and Z-VAD-FMK control. Mean ± SD; n=3 replicates, representative of three independent experiments. — Figure 5a–d and caption; corresponding Results and Online Methods

BAI1 reduces SASP-factor secretion in irradiated human fibroblasts

Cell-based study · MRC5 human fibroblasts after 20 Gy X-ray-induced senescence; proliferating and senescent vehicle controls. [2]

BAI1 treatment reduced secreted IL-6, IL-8 and IP-10 in a concentration-dependent series in senescent MRC5 fibroblasts. Responses differed by cytokine and concentration; the low-dose IL-8 comparison was not significant. These endpoints characterize the secretory phenotype, not elimination of senescent cells.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Secreted IL-6, IL-8 and IP-10 from MRC5 fibroblasts	Fold change to proliferating controls; qualitative direction Reduced secretion across the tested BAI1 series; IL-8 at 0.1 μM: P=0.06	[2]

Literature-Reported Treatment Conditions

Treatment concentration: BAI1 0.1, 1 and 2.5 μM, as labeled in Extended Data Figure 9f.
Exposure duration: Added immediately after irradiation and maintained for 10 days; refreshed every 48–72 h.
Method: Cell-culture treatment following 20 Gy X-ray irradiation.
Vehicle: DMSO vehicle control.
Co-treatment: No other pharmacological treatment in the adopted secretion experiment.
Reported limits: The reviewed methods list multiplex and confirmatory ELISA measurements without assigning each plotted cytokine value to one platform; final DMSO percentage is not identified.

Methods and source locations

Compound reported in the paper: BAI1 (Bax channel blocker); Compound label in the paper: BAI1

These fibroblast results are directly linked to catalog A15335 in the paper; they are not analytical validation of a current lot.

Extended Data Figure 9f and caption; Methods: Cell culture and treatments; Cytokine array

Secreted IL-6, IL-8 and IP-10 from MRC5 fibroblasts: Extended Data Figure 9f heatmap; n=4 independent experiments, mean fold change. Methods lists supernatant cytokine multiplex assays and confirmatory cytokine-specific ELISAs. No exact fold changes estimated from the heatmap. — Extended Data Figure 9f and caption; Methods: Cell culture and treatments; Cytokine array

In Vivo Studies

In aged C57BL/6 mice, BAI1 (Tocris 2160; 10 mg/kg intraperitoneally, three times weekly for three months) improved rotarod, pole and forelimb hanging-test outcomes versus vehicle. A separate cohort treated from 18–20 months old until death showed no significant lifespan benefit. These findings apply to the reported mouse models and tested material. [2]

Functional outcomes after three months of BAI1 in aged mice

Animal study · Aged wild-type C57BL/6 mice, both sexes; 18–20 months at study entry in Methods/Figure 6c. Random assignment to vehicle or BAI1. [2]

After three months of BAI1 treatment, aged mice had increased rotarod latency and improved performance in pole and forelimb hanging tests versus vehicle controls. Endpoint-specific cohort sizes differ. These are mouse functional outcomes; they do not establish human efficacy or lifespan extension.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Rotarod latency to fall	Qualitative improvement Increased latency versus vehicle (P=0.0005)	[2]
Time on raised pole and success in forelimb hanging test	Qualitative functional outcomes Improved pole performance and forelimb hanging success	[2]

Conditions shared by the study groups

Route: Intraperitoneal injection
Frequency: Three times weekly
Treatment course: Three months

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
BAI1-treated aged mice 10 mg/kg	Vehicle-treated aged mice	Improved rotarod, pole and hanging-test performance; endpoint-specific n values retained in measurements.	[2]

BAI1-treated aged mice: Model: Aged wild-type C57BL/6 mice, male and female; Reported limits: Vehicle composition and salt are not stated in the reviewed original animal methods; no dose conversion performed.

Methods and source locations

Compound reported in the paper: BAI1 (Bax channel blocker); Compound label in the paper: BAI1

Animal results concern the reported Tocris BAI1 material and regimen. No salt conversion, formulation equivalence or Adooq lot validation is inferred.

Figure 6c–e and caption; Methods: Mouse models and treatments; Rotarod tests; Forelimb grip strength analysis (hanging test); Neuromuscular coordination analysis

Rotarod latency to fall: Mean ± SEM; vehicle n=13 mice, BAI1 n=17 mice; two-sided unpaired Student’s t-test. Rotarod outcome averaged three trials per mouse. No exact latency extracted from points. — Figure 6c and caption; Methods: Mouse models and treatments; Rotarod tests

Time on raised pole and success in forelimb hanging test: Vehicle n=7 mice and BAI1 n=8 mice for Figure 6d,e. Pole: mean ± SEM, two-way ANOVA with Sidak comparisons. Hanging: up to 10 attempts to accumulate 90 s, percentage success shown. — Figure 6d,e and caption; Methods: Mouse models and treatments; Forelimb grip strength analysis (hanging test); Neuromuscular coordination analysis

BAI1-treated aged mice · Figure 6c–e; Methods: Mouse models and treatments

No lifespan benefit with continued BAI1 in aged mice

Animal study · Wild-type C57BL/6 mice starting treatment at 18–20 months, followed until death or humane endpoint. [2]

Continued BAI1 treatment did not significantly alter lifespan compared with vehicle. This separate survival design limits interpretation of functional improvements as lifespan extension.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Survival after treatment initiation in aged mice	Kaplan–Meier survival No significant lifespan effect	[2]

Conditions shared by the study groups

Route: Intraperitoneal injection
Frequency: Three times weekly
Treatment course: From 18–20 months old until death

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
BAI1-treated survival cohort 10 mg/kg	Vehicle-treated mice (n=38)	No significant lifespan extension.	[2]

BAI1-treated survival cohort: Model: Aged wild-type C57BL/6 mice, n=39 BAI1 and n=38 vehicle; Reported limits: Vehicle composition and salt are not stated in the reviewed original animal methods; no dose conversion performed.

Methods and source locations

Compound reported in the paper: BAI1 (Bax channel blocker); Compound label in the paper: BAI1

Animal results concern the reported Tocris BAI1 material and regimen. No salt conversion, formulation equivalence or Adooq lot validation is inferred.

Extended Data Figure 10b and caption; Methods: Mouse models and treatments; corresponding ageing Results

Survival after treatment initiation in aged mice: Vehicle n=38 mice; BAI1 n=39 mice. Methods specifies right-censored Kaplan–Meier analysis and log-rank test. The viewed main/extended-data material does not give an exact survival P value or median effect size; none is inferred from the curve. — Extended Data Figure 10b and caption; Results: Inhibiting MOMP improves healthspan; Methods: Mouse models and treatments

BAI1-treated survival cohort · Extended Data Figure 10b; Methods: Mouse models and treatments

Specifications

Manufacturer	Adooq Bioscience
Actions	Inhibitor, Blocker
CAS Number	335165-68-9
Applications	Bax channel blocker
Formula	C₁₉H₂₃Br₂Cl₂N₃O
Molecular Weight	540.12
SMILES	C1CN(CCN1)CC(CN2C3=C(C=C(C=C3)Br)C4=C2C=CC(=C4)Br)O.Cl.Cl

Storage & Solubility

In Vitro Solubility

Reported Solubility

Solvent	Reported Solubility
DMSO	17 mg/mL (36.38 mM)
Water	Insoluble
Ethanol	3 mg/mL (6.42 mM)

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

[1] Garner TP, Amgalan D, Reyna DE, et al. Small-molecule allosteric inhibitors of BAX. Nature chemical biology (2019). PMID: 30718816 DOI: 10.1038/s41589-018-0223-0 Source material
[2] Victorelli S, Salmonowicz H, Chapman J, et al. Apoptotic stress causes mtDNA release during senescence and drives the SASP. Nature (2023). PMID: 37821702 DOI: 10.1038/s41586-023-06621-4 Source material

Publications

1 publication citing this product

Stella Victorelli, .et al. , Nature, 2023, Oct;622(7983):627-636 PMID: 37821702

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Bax channel blocker

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