| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
calcium ionophore
Calcium ions (Ca2+) as a mobile ion carrier; also copper ions (Cu2+) as a copper ionophore. |
|---|---|
| ln Vitro |
Increase in intracellular calcium concentrations ([Ca2+]i) is critical for the initiation of apoptosis in cells such as thymocytes and in other cells, calcium chelators may promote apoptosis. However, calcium modulators, such as calcium ionophore 4-bromo-calcium ionophore (Br-A23187) and thapsigargin (TG), induce apoptosis in different cells, including HL-60 cells in which the induction of apoptosis seems a calcium-independent process. These observations imply that the disturbance of calcium homeostasis is probably the most important factor in the regulation of apoptosis. In this article, reagents with different potencies of modulating calcium homeostasis were used to study the possible role of [Ca2+]i and the status of intracellular calcium stores in the causation of HL-60 cell apoptosis. We found that an increase in [Ca2+]i alone did not result in apoptosis, while the depletion of TG-sensitive calcium stores in the endoplasmic reticulum was closely related with the induction of apoptosis. In HL-60 cells, extracellular and intracellular calcium chelators promoted apoptosis. Calmodulin antagonist did not attenuate apoptosis induced by other reagents. Our results suggest that the depletion of Ca2+ stores is an important mean to modulate calcium homeostasis and that the mobilization of calcium (Ca2+) from intracellular stores, rather than an increase in [Ca2+]i, provides the signal for the induction of apoptosis in HL-60 cells.[1]
In vitro, 4-Bromo A23187 increases intracellular Ca2+ levels by facilitating the transport of calcium across cell membranes. It has been used to activate Ca2+/calmodulin-dependent protein kinase II (CaMKII) in HeLa cells. The compound also functions as a calcium mobilizer to investigate the effect of calcium signaling on superoxide dismutase 1 (SOD1) aggregates in VSC 4.1 cells. As a copper ionophore, 4-Bromo A23187 increases intracellular copper levels, leading to oxidative stress, disruption of metal homeostasis, and antibacterial effects against Bacillus subtilis. It modulates apoptosis in a concentration-dependent manner. |
| ln Vivo |
In vivo, 4-Bromo A23187 is primarily used as an ex vivo tool rather than for systemic in vivo administration. It has been used in studies on thymic lymphocytes to saturate Ca2+ binding sites and calibrate cytoplasmic free Ca2+ measurements. The compound's utility in vivo is limited by its ionophore properties and potential for disrupting systemic calcium homeostasis. No specific in vivo efficacy data are reported for this analog.
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| Enzyme Assay |
Ionophore activity is assessed using artificial lipid bilayer membranes or liposome-based assays. Calcium transport is measured by monitoring fluorescence changes of calcium-sensitive dyes (e.g., Fluo-4, Fura-2, or Quin-2) in the presence of the ionophore. For receptor/ionophore binding studies, the compound is incubated with calcium-loaded vesicles or cells, and the rate of calcium efflux or influx is measured spectrophotometrically or fluorometrically. Copper ionophore activity is evaluated using copper-sensitive fluorescent probes or by measuring intracellular copper accumulation via atomic absorption spectroscopy. Antibacterial activity is assessed by minimum inhibitory concentration (MIC) determination against bacterial strains such as Bacillus subtilis.
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| Cell Assay |
Cells (e.g., HeLa, VSC 4.1, HL-60, or thymic lymphocytes) are cultured in appropriate medium and loaded with calcium-sensitive fluorescent dyes (e.g., Fluo-4 AM, Fura-2 AM, or Quin-2 AM) at 2-5 microM for 30-60 minutes at 37degC. After washing, cells are treated with 4-Bromo A23187 at concentrations ranging from 0.1-10 microM. Intracellular calcium levels are measured by monitoring fluorescence intensity (excitation/emission wavelengths appropriate for the dye used) in real-time using a fluorescence plate reader or flow cytometer. For apoptosis studies, HL-60 cells are treated with the compound and apoptosis is quantified using Annexin V/PI staining or caspase activity assays. For CaMKII activation studies, cells are treated and phosphorylation of CaMKII substrates is assessed by Western blot.
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| Animal Protocol |
In vivo studies are limited due to the compound's ionophore properties. When used, 4-Bromo A23187 is typically administered locally or used in ex vivo tissue preparations. For thymic lymphocyte studies, cells are isolated from rat thymus, loaded with Quin-2, and treated with the ionophore to calibrate calcium measurements. No standardized in vivo animal protocols are established for this compound. For antibacterial studies, the compound may be tested in localized infection models, though such applications are primarily in vitro.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for 4-Bromo A23187 are not extensively reported. As an ionophore, the compound is expected to have limited systemic bioavailability due to its lipophilic nature and potential for rapid distribution into cell membranes. The compound is soluble in ethanol (20 mg/mL) and DMSO, and is typically stored at 2-8degC. Its non-fluorescent property makes it suitable for use with fluorescent probes without spectral interference. Metabolism and elimination pathways are presumed to be similar to the parent compound A23187.
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| Toxicity/Toxicokinetics |
The compound is classified as an irritant with potential for acute toxicity. Hazard classifications include Acute Toxicity (oral, dermal, inhalation), Eye Irritant, Skin Irritant, and Specific Target Organ Toxicity (respiratory system). Appropriate personal protective equipment (dust mask N95, eyeshields, gloves) should be used when handling. The compound is for research use only and not for human or veterinary therapeutic use. Safety data should be reviewed before use.
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| References | |
| Additional Infomation |
See also: 4-Bromo-A-23187 (Note has been moved to).
4-Bromo A23187 is a non-fluorescent analog of the calcium ionophore A23187, designed specifically for experiments employing fluorescent probes to avoid interference. It serves as a calibration standard for determining cytoplasmic calcium ion concentrations. The compound has molecular formula C2₉H3₆BrN3O₆ and molecular weight 602.53. It is available as a yellow powder. In addition to its calcium ionophore activity, 4-Bromo A23187 has been identified as a potent copper ionophore with significant antibacterial effects, representing a distinct mechanism of action. It induces apoptosis in certain cell lines such as HL-60 cells. |
| Molecular Formula |
C29H36N3O6BR
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|---|---|
| Molecular Weight |
602.51664
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| Exact Mass |
601.179
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| Elemental Analysis |
C, 57.81; H, 6.02; Br, 13.26; N, 6.97; O, 15.93
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| CAS # |
76455-48-6
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| Related CAS # |
Calcimycin hemicalcium salt;59450-89-4;Calcimycin hemimagnesium;72124-77-7; 76455-48-6 (bromo); 52665-69-7
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| PubChem CID |
16211362
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| Appearance |
White to yellow solid powder
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| Density |
1.43g/cm3
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| Boiling Point |
735.4ºC at 760 mmHg
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| Flash Point |
398.5ºC
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| Index of Refraction |
1.628
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| LogP |
6.365
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
39
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| Complexity |
910
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C[C@@H]1CC[C@]2([C@@H](C[C@H]([C@H](O2)[C@H](C)C(=O)C3=CC=CN3)C)C)O[C@@H]1CC4=NC5=C(C(=C(C=C5O4)Br)NC)C(=O)O
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| InChi Key |
LDXQFZZGVTWFCF-FHYGWRBKSA-N
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| InChi Code |
InChI=1S/C29H36BrN3O6/c1-14-8-9-29(16(3)11-15(2)27(39-29)17(4)26(34)19-7-6-10-32-19)38-20(14)13-22-33-25-21(37-22)12-18(30)24(31-5)23(25)28(35)36/h6-7,10,12,14-17,20,27,31-32H,8-9,11,13H2,1-5H3,(H,35,36)/t14-,15-,16-,17-,20-,27+,29+/m1/s1
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| Chemical Name |
6-bromo-5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid
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| Synonyms |
4-Bromo-A23187; 76455-48-6; 4-Bromo-antibiotic; 4-Bromo A23187; 4-Bromo-calcium Ionophore A23187; MFCD00077667; 4-Bromo-calcimycin; 6-bromo-5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid;
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6597 mL | 8.2985 mL | 16.5970 mL | |
| 5 mM | 0.3319 mL | 1.6597 mL | 3.3194 mL | |
| 10 mM | 0.1660 mL | 0.8298 mL | 1.6597 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.
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