| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
Purity: =98.71%
| Targets |
Mito-LND targets mitochondria and inhibits oxidative phosphorylation (OXPHOS) by disrupting respiratory complexes I and II. It potently inhibits mitochondrial bioenergetics, stimulates the formation of reactive oxygen species (ROS), and induces autophagic cell death in cancer cells. The compound selectively accumulates in cancer cell mitochondria due to their high membrane potential, which reduces systemic toxicity compared to non-targeted agents.
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| ln Vitro |
Mito-LND inhibits the invasion, migration, and development of lung cancer. H2030BrM3 and A549 cells' proliferation is inhibited by mito-LND, with IC50 values of 0.74 µM and 0.69 µM, respectively[1]. In H2030BrM3 cells, mito-LND suppresses the activities of mitochondrial complex I and II with IC50 values of 1.2 µM and 2.4 µM, respectively[1]. ROS production in H2030BrM3 lung cancer cells is increased by mito-LND (1 µM). In H2030BrM3 lung cancer cells, Mito-LND potently promotes mitochondrial ROS generation[1]. Mito-LND (2 µM) lowers phosphorylated AKT levels. In both the parent and metastatic lung cancer cell lines, Mito-LND also reduces the phosphorylation of P70S6K and other energy-sensing proteins, suggesting that Mito-LND directly inhibits mTOR signaling[1].
Mito-LND inhibits mitochondrial bioenergetics and stimulates ROS formation in lung cancer cells. It induces autophagic cell death in various cancer cell lines. As a mitochondria-targeted derivative of lonidamine, Mito-LND is significantly more potent and selective in targeting cancer cells by disrupting their mitochondrial function. At low micromolar concentrations, it is a potent inhibitor of cancer cell mitochondrial bioenergetics. |
| ln Vivo |
Treatment with mito-LND (7.5 µmol/kg; oral gavage; 5 days per week; for 3 consecutive weeks) significantly increased potency against the progression and metastasis of lung cancer[1]. Additionally, A549 tumor xenografts develop less quickly when treated with mito-LND [1]. When NOD/SCID mice containing H2030BrM3 cells get mito-LND therapy, lung cancer brain metastases significantly decrease[1].
In vivo, Mito-LND demonstrates potent antitumor activity in preclinical models. Oral gavage administration (5 days per week for 3 consecutive weeks) markedly enhances potency. The compound has shown pronounced mitigation of lung cancer development, cell proliferation, growth, progression, and metastasis. Its selective mitochondrial accumulation reduces systemic toxicity, making it a promising candidate for mitochondrial-targeted cancer therapy. |
| Enzyme Assay |
Mitochondrial bioenergetics assays are performed using isolated mitochondria or intact cancer cells. Oxygen consumption rate (OCR) is measured using Seahorse XF analyzers to assess mitochondrial respiration. Mito-LND is incubated with cells or isolated mitochondria at various concentrations, and parameters such as basal respiration, ATP production, and maximal respiratory capacity are measured. ROS production is quantified using fluorescent probes such as DCFH-DA or MitoSOX.
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| Cell Assay |
Cancer cell lines (e.g., lung cancer cells) are seeded in multi-well plates and treated with varying concentrations of Mito-LND for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Autophagic cell death is evaluated by monitoring LC3-II accumulation, autophagosome formation, and measuring cell death markers. ROS levels are quantified using fluorescent probes. Mitochondrial membrane potential is assessed using JC-1 dye.
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| Animal Protocol |
Animal/Disease Models: Athymic nude mice (5 weeks) injected with H2030BrM3 cells[1]
Doses: 7.5 µmol/kg Route of Administration: po (oral gavage); 5 days per week; for 3 consecutive weeks Experimental Results: Dramatically diminished tumor progression. In vivo efficacy is evaluated in murine xenograft models using human cancer cell lines. Tumor-bearing mice are treated with Mito-LND via oral gavage at various doses (5 days per week for 3 consecutive weeks). Tumor volumes are measured every 2-3 days. Body weight and clinical signs are monitored for tolerability. Tumor tissues are collected for analysis of mitochondrial function, ROS levels, and markers of autophagic cell death. The compound's antitumor activity and metastasis inhibition are assessed. |
| ADME/Pharmacokinetics |
Mito-LND is orally active with good bioavailability. It has a molecular weight of 801.62 and molecular formula C43H45BrCl2N3OP. The compound is soluble in DMSO and other organic solvents. The TPP+ cation moiety enables selective accumulation in mitochondria due to the high membrane potential of cancer cells. For in vivo studies, appropriate oral formulations are required.
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| Toxicity/Toxicokinetics |
Mito-LND's selective mitochondrial accumulation reduces systemic toxicity compared to non-targeted lonidamine. The compound has been evaluated in preclinical models with acceptable tolerability. As an OXPHOS inhibitor targeting mitochondrial bioenergetics, potential toxicities may include effects on normal tissues with high energy demands. Standard safety pharmacology and toxicology studies would be required for clinical development. The compound should be handled with appropriate laboratory safety precautions.
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| References | |
| Additional Infomation |
Mito-LND is also known as Mito-Lonidamine. It is a mitochondria-targeted derivative of lonidamine conjugated with a triphenylphosphonium cation. The compound selectively accumulates in cancer cell mitochondria due to their high membrane potential and potently inhibits OXPHOS by disrupting respiratory complexes I and II. Mito-LND is being investigated for cancer therapy, particularly for lung cancer and prostate cancer.
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| Molecular Formula |
C43H45BRCL2N3OP
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| Molecular Weight |
801.6207
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| Exact Mass |
799.186
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| CAS # |
2361564-49-8
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| PubChem CID |
155977659
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| Appearance |
Off-white to light yellow 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 |
17
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| Heavy Atom Count |
51
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| Complexity |
938
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[Br-].ClC1C([H])=C(C([H])=C([H])C=1C([H])([H])N1C2=C([H])C([H])=C([H])C([H])=C2C(C(N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[P+](C2C([H])=C([H])C([H])=C([H])C=2[H])(C2C([H])=C([H])C([H])=C([H])C=2[H])C2C([H])=C([H])C([H])=C([H])C=2[H])=O)=N1)Cl
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| InChi Key |
XRSSFQSESARZNG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C43H44Cl2N3OP.BrH/c44-35-29-28-34(40(45)32-35)33-48-41-27-17-16-26-39(41)42(47-48)43(49)46-30-18-5-3-1-2-4-6-19-31-50(36-20-10-7-11-21-36,37-22-12-8-13-23-37)38-24-14-9-15-25-38;/h7-17,20-29,32H,1-6,18-19,30-31,33H2;1H
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| Chemical Name |
10-[[1-[(2,4-dichlorophenyl)methyl]indazole-3-carbonyl]amino]decyl-triphenylphosphanium;bromide
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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, 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 : 50 mg/mL (62.37 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2475 mL | 6.2374 mL | 12.4747 mL | |
| 5 mM | 0.2495 mL | 1.2475 mL | 2.4949 mL | |
| 10 mM | 0.1247 mL | 0.6237 mL | 1.2475 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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