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| Targets |
MitoTam bromide, hydrobromide targets the mitochondrial electron transport chain (ETC), specifically inhibiting respiratory complex I (CI-respiration) and disrupting respiratory supercomplexes (SCs) formation in breast cancer cells. By inhibiting ETC function, the compound disrupts mitochondrial bioenergetics. The triphenylphosphonium moiety facilitates accumulation in mitochondria, enabling selective targeting of cancer cell mitochondria while minimizing effects on normal cells.
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| ln Vitro |
With an IC50 range of 0.65 μM to 55.9 μM, MitoTam (0.5 μM-56 μM; 24 hours) kills nonmalignant cells and breast cancer cell lines[1]. When compared to mock MCF7 cells, MitoTam (2.5 μM; 2-24 hours) causes a greater activation of the apoptotic pathway in MCF7 Her2 high cells[1]. Breast cancer cells undergo a concentration-dependent activation of apoptosis upon exposure to MitoTam (0.05 μM-1 μM; 3 days); non-malignant breast epithelial cells were unaffected[2].
MitoTam bromide, hydrobromide demonstrates potent in vitro anticancer activity. It suppresses respiratory complexes and disrupts respiratory supercomplexes formation in breast cancer cells. The compound kills breast cancer cell lines and non-malignant cells at concentrations ranging from 0.5-56 microM. MitoTam results in stronger activation of the apoptotic pathway in MCF7 Her2high cells compared with mock MCF7 cells. The compound shows selectivity for cancer cells. |
| ln Vivo |
When compared to control mice, MitoTam (intraperitoneal injection; 2 μg/g; once a week; 4 weeks) reduces the amount of β-gal staining in the lungs of the mice treated with it. This is accompanied by a suppression of the expression of senescence markers p16Ink4a, p21waf1, and PAI [2]. MitoTam, an intraperitoneal injection administered twice a week for two weeks at a dose of 0.54 μmol/mouse, reduces syngeneic tumor growth by 80%[1]. MitoTam, an intraperitoneal injection administered twice a week for two weeks at a concentration of 0.25 μmol/mouse, suppresses Her2high carcinomas, causing them to shrink three times their initial size and eventually disappear[1].
In vivo, MitoTam bromide, hydrobromide demonstrates anticancer activity as a mitochondria-targeted therapeutic agent. The compound's mechanism involves disruption of mitochondrial function in cancer cells, leading to reduced tumor growth. It shows strong anticancer activity with minimal effects on normal cells. The compound is widely used in studies of mitochondrial metabolism and cancer therapeutics. As a tamoxifen derivative, it may share some pharmacological properties with tamoxifen. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for MitoTam bromide, hydrobromide typically involve assessment of mitochondrial respiratory complex activity. Complex I activity is measured spectrophotometrically by following NADH oxidation. Respiratory supercomplex formation is assessed by Blue Native PAGE (BN-PAGE) followed by in-gel activity staining or Western blotting. Mitochondrial membrane potential is measured using fluorescent probes such as JC-1 or TMRM.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: Breast Cancer Cell Types: BT474, MCF7, MCF7 Her2high, MCF7 Her2low, MDA-MB-231, MDA-MB-436, MDA-MB-453, SK-BR- 3, T47D; NeuTL cells; Nonmalignant Cells: A014578, H9c2 cells Tested Concentrations: 0.5 μM-56 μM Incubation Duration: 24 hrs (hours) Experimental Results: Killed breast cancer cells MCF7, MCF7 Her2high, MCF7 Her2low with IC50 values of 1.25 μM, 0.65 μM and 1.45 μM respectively. Western Blot Analysis[1] Cell Types: MCF7 mock cells, MCF7 Her2high cells Tested Concentrations: 2.5 μM Incubation Duration: 2 hrs (hours), 4 hrs (hours), 8 hrs (hours), 16 hrs (hours), 24 hrs (hours) Experimental Results: Revealed accelerated cleavage of procaspase-9, Parp1/2 and proapoptotic Bax, diminished the antiapoptotic Bcl-2 protein in Her2high cells. Apoptosis Analysis[2] Cell Types: MCF-7 cells, 4T1 cells and MCF-10a cells Tested Concentrations: 0.05 μM-1 μM Incubation Duration: 3 days Experimental Results: Resulted in apoptosis in MCF7 and 4T1 cells. In vitro cellular assays for MitoTam bromide, hydrobromide involve treating cancer cell lines (e.g., MCF7, MCF7 Her2high) with varying concentrations (typically 0.5-56 microM range) for 24-72 hours. Readouts include cell viability measured by MTT or similar assays, apoptosis assessment via annexin V/PI staining or caspase activity assays, mitochondrial membrane potential measurement using fluorescent probes, and mitochondrial morphology analysis by microscopy. |
| Animal Protocol |
Animal/Disease Models: 18-month-old or 2-month-old FVB/N mice [2]
Doses: 2 μg/g Route of Administration: intraperitoneal (ip)injection; 2 μg/g; once a week; 4 weeks Experimental Results: Eliminated senescent cells also in vivo. Animal/Disease Models: FVB/N c-neu mouse[1] Doses: 0.54 μmol/mouse Route of Administration: intraperitoneal (ip)injection; 0.54 μmol/mouse; twice a week; 2 weeks Experimental Results: Suppressed Her2high breast carcinomas. Animal/Disease Models: Balb/c nude mice with MCF7 mock or MCF7 Her2high cells[1] Doses: 0.25 μmol/mouse /dose Route of Administration: intraperitoneal (ip)injection; 0.25 μmol/mouse/dose; twice a week; 2 weeks Experimental Results: Prevented reaching the ethical endpoint in all situations, slowed down the growth of MCF7 mock tumors and suppressed Her2high carcinomas diminished. In vivo animal studies for MitoTam bromide, hydrobromide typically employ xenograft mouse models bearing breast cancer tumors. Tumor-bearing mice are administered the compound via appropriate routes at various dose levels. Tumor growth is monitored over 2-4 weeks with endpoints including tumor volume measurements, body weight monitoring, and survival analysis. Mitochondrial function in tumor tissue may be assessed ex vivo. The compound's selectivity for cancer cells suggests a favorable therapeutic window. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of MitoTam bromide, hydrobromide are characteristic of mitochondria-targeted compounds. The triphenylphosphonium moiety facilitates accumulation in mitochondria, which may affect distribution and elimination. The compound is typically stored at -20degC. PK parameters would be determined via LC-MS/MS analysis. The bromide hydrobromide salt form provides specific pharmaceutical properties. Bioavailability depends on formulation and route of administration.
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| Toxicity/Toxicokinetics |
Toxicological data for MitoTam bromide, hydrobromide indicates that it is a research-grade compound. As a tamoxifen derivative and ETC inhibitor, potential toxicities may include mitochondrial dysfunction-related effects. The compound shows minimal effects on normal cells, suggesting a favorable safety profile. Standard safety precautions should be observed during handling including appropriate PPE and work in a fume hood. Comprehensive toxicology studies are not publicly available.
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| References | |
| Additional Infomation |
MitoTam bromide, hydrobromide (CAS# 1634624-73-9) is a mitochondria-targeted tamoxifen derivative. It is also known as MitoTam and is a novel anticancer agent. The compound is designed to selectively disrupt mitochondrial function in cancer cells with minimal effects on normal cells. It is widely used in research on mitochondrial metabolism and cancer therapeutics. The bromide hydrobromide salt form provides specific pharmaceutical properties. The compound is not approved for clinical use and is for research purposes only.
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| Molecular Formula |
C52H59BRNOP
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| Molecular Weight |
824.908734560013
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| Exact Mass |
905.275
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| CAS # |
1634624-73-9
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| Related CAS # |
MitoTam iodide, hydriodide;1634624-74-0
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| PubChem CID |
86304737
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
21
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| Heavy Atom Count |
57
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| Complexity |
984
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[P+](C1C=CC=CC=1)(C1C=CC=CC=1)(C1C=CC=CC=1)CCCCCCCCCC/C(/C1C=CC=CC=1)=C(\C1C=CC=CC=1)/C1C=CC(OCCN(C)C)=CC=1.[Br-]
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| InChi Key |
LKYHAJFFVLTBRB-DRFCFMONSA-M
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| InChi Code |
InChI=1S/C52H59NOP.2BrH/c1-53(2)41-42-54-47-39-37-46(38-40-47)52(45-28-16-10-17-29-45)51(44-26-14-9-15-27-44)36-24-7-5-3-4-6-8-25-43-55(48-30-18-11-19-31-48,49-32-20-12-21-33-49)50-34-22-13-23-35-50;;/h9-23,26-35,37-40H,3-8,24-25,36,41-43H2,1-2H3;2*1H/q+1;;/p-1/b52-51-;;
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| Chemical Name |
[(Z)-12-[4-[2-(dimethylamino)ethoxy]phenyl]-11,12-diphenyldodec-11-enyl]-triphenylphosphanium;bromide;hydrobromide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO : ~240 mg/mL (~264.95 mM)
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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 | 1.2123 mL | 6.0613 mL | 12.1225 mL | |
| 5 mM | 0.2425 mL | 1.2123 mL | 2.4245 mL | |
| 10 mM | 0.1212 mL | 0.6061 mL | 1.2123 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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