| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Myxothiazol targets the mitochondrial cytochrome bc1 complex (Complex III), a key component of the electron transport chain. It binds with high affinity to the quinol oxidation (Qo) site of the bc1 complex, blocking electron transfer to the Rieske iron-sulfur protein. This inhibition disrupts the flow of electrons from ubiquinol to cytochrome c1, halting the generation of the proton gradient necessary for ATP synthesis. By inhibiting Complex III, Myxothiazol induces mitochondrial dysfunction and triggers cellular stress responses, including the transcription of the p53-responsive SESN2 gene, which plays a role in stress response and homeostatic regulation.
|
|---|---|
| ln Vitro |
Many yeasts and fungi are inhibited from growing when myxothiazol is present at quantities ranging from 0.01 to 3 μg/ml [2]. Complex III's ubiquinol oxidation site Qo is bound by myxothiazol, which prevents ubiquinol from transferring its electrons to cytochrome b and hence reduces complex III's activity [3].
In vitro, Myxothiazol inhibits mitochondrial respiration in isolated mitochondria and in cell-based systems. It inhibits the growth of many yeasts and fungi in the concentration range of 0.01~3 μg/ml. In mammalian cells, Myxothiazol treatment leads to decreased ATP production, increased reactive oxygen species (ROS) production, and induction of cellular stress responses. The compound's inhibitory activity on Complex III is typically assessed by measuring oxygen consumption rates or by monitoring the reduction of cytochrome c in isolated mitochondria. Myxothiazol is a widely used tool for studying mitochondrial function and the role of the electron transport chain in cellular physiology and disease. |
| ln Vivo |
In mice, myxothiazol (ip; 0.56 mg/kg; once daily for four days) causes complex III inhibition for four days in a row without causing appreciable hepatotoxicity or mortality [3].
In vivo, Myxothiazol has been used as an antibiotic in research settings, but its therapeutic use is limited due to its toxicity to mammalian cells. The compound's antifungal activity has been demonstrated in animal models of fungal infection, but its systemic toxicity precludes clinical use. Myxothiazol's effects on mitochondrial respiration in vivo would be expected to cause significant toxicity, including neurotoxicity, cardiotoxicity, and hepatotoxicity. The compound is primarily used as a research tool for studying mitochondrial function in isolated systems and in cell culture. It has not been developed for clinical applications due to its narrow therapeutic window. |
| Enzyme Assay |
In vitro enzyme assays for Myxothiazol involve measuring the inhibition of the cytochrome bc1 complex (Complex III) activity in isolated mitochondria or in purified enzyme preparations. A typical protocol: mitochondria are isolated from bovine heart or rat liver by differential centrifugation. Mitochondrial membranes are incubated with varying concentrations of Myxothiazol (0.1 nM to 10 μM) in assay buffer (50 mM potassium phosphate, pH 7.4, 1 mM EDTA, 0.1% BSA). The reaction is initiated by the addition of decylubiquinol (50 μM) and cytochrome c (50 μM). The reduction of cytochrome c is monitored spectrophotometrically at 550 nm. IC₅₀ values are calculated from inhibition curves. Positive controls include antimycin A or stigmatellin. Each concentration is tested in triplicate, and experiments are repeated at least three times.
|
| Cell Assay |
In vitro cell-based assays for Myxothiazol are performed using mammalian cell lines such as HeLa, HEK293, or primary neurons. A typical protocol: cells are seeded in 96-well plates at 10,000-20,000 cells/well and cultured for 24 hours. Cells are treated with Myxothiazol at concentrations ranging from 0.01 to 10 μM for 2-24 hours. Mitochondrial function is assessed by measuring oxygen consumption rate (OCR) using a Seahorse analyzer or by measuring ATP levels using a luciferase-based assay. ROS production is measured using DCFH-DA or MitoSOX staining followed by flow cytometry or fluorescence microscopy. Cell viability is assessed using MTT or CellTiter-Glo assays. Each condition is tested in triplicate, and experiments are repeated at least three times. Positive controls include rotenone or antimycin A.
|
| Animal Protocol |
Animal/Disease Models: C57Bl/J6 mice [3]
Doses: 0.56 mg/kg Route of Administration: intraperitoneal (ip) injection; 24 hrs (hrs (hours)) apart, up to 4 times Experimental Results: 2 hrs (hrs (hours)) after injection, complex III activity reversibly diminished to 50% of the control value . At 74 hrs (hrs (hours)), only minor histological changes were found in the liver, supercomplex formation was preserved, and no significant changes in gene expression indicative of hepatotoxicity or inflammation were found. In vivo animal studies for Myxothiazol are limited due to its toxicity. If conducted, a typical protocol would involve administering Myxothiazol to mice via intraperitoneal injection at doses of 0.1-5 mg/kg. However, significant toxicity would be expected at these doses due to mitochondrial inhibition. The compound is not suitable for in vivo studies in mammals due to its narrow therapeutic window. It is primarily used as a research tool for in vitro studies of mitochondrial function. The compound has not been evaluated in preclinical efficacy models for therapeutic applications. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Myxothiazol have not been characterized due to its toxicity and lack of clinical development. As a lipophilic compound, it is expected to have good membrane permeability but poor oral bioavailability. The compound is likely to be rapidly distributed to tissues, particularly those with high mitochondrial content (e.g., heart, liver, brain). Its metabolism and elimination have not been studied. The compound is for research use only and is not intended for human use. It should be stored at -20°C for long-term stability.
|
| Toxicity/Toxicokinetics |
Toxicological data for Myxothiazol are limited. As a mitochondrial inhibitor, it is expected to be toxic to mammalian cells and organisms. The compound's mechanism of action—inhibition of the electron transport chain—would result in cellular energy depletion, oxidative stress, and cell death. The compound is not suitable for therapeutic use due to its narrow therapeutic window. Standard laboratory safety precautions should be followed when handling Myxothiazol: use of personal protective equipment (gloves, safety goggles, lab coat) and handling in a well-ventilated fume hood. The compound should be stored at -20°C for long-term stability. Researchers should consult the safety data sheet (SDS) before handling.
|
| References |
|
| Additional Infomation |
Reports indicate that Myxothiazol and bees contain myxobolus and myxobolus, and relevant data are available for reference.
Additional information for Myxothiazol: The compound has a CAS number of 76706-55-3. It is an antifungal antibiotic produced by Myxococcus fulvus. It is a potent, competitive inhibitor of the mitochondrial cytochrome bc1 complex (Complex III). It binds to the Qo site of the bc1 complex, blocking electron transfer to the Rieske iron-sulfur protein. It inhibits the growth of many yeasts and fungi at 0.01-3 μg/ml. The compound is for research use only and is not approved for clinical applications. No FDA approvals exist. |
| Molecular Formula |
C25H33N3O3S2
|
|---|---|
| Molecular Weight |
487.67782
|
| Exact Mass |
487.196
|
| CAS # |
76706-55-3
|
| PubChem CID |
10972974
|
| Appearance |
White to off-white solid powder
|
| Density |
1.158g/cm3
|
| Boiling Point |
679.6ºC at 760 mmHg
|
| Flash Point |
364.8ºC
|
| Index of Refraction |
1.584
|
| LogP |
6.518
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
33
|
| Complexity |
738
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
C[C@@H](/C=C/C=C/C(C)C)C1=NC(=CS1)C2=NC(=CS2)/C=C/[C@@H]([C@@H](C)/C(=C\C(=O)N)/OC)OC
|
| InChi Key |
XKTFQMCPGMTBMD-FYHMSGCOSA-N
|
| InChi Code |
InChI=1S/C25H33N3O3S2/c1-16(2)9-7-8-10-17(3)24-28-20(15-33-24)25-27-19(14-32-25)11-12-21(30-5)18(4)22(31-6)13-23(26)29/h7-18,21H,1-6H3,(H2,26,29)/b9-7+,10-8+,12-11+,22-13+/t17-,18+,21-/m0/s1
|
| Chemical Name |
(2E,4R,5S,6E)-3,5-dimethoxy-4-methyl-7-[2-[2-[(2S,3E,5E)-7-methylocta-3,5-dien-2-yl]-1,3-thiazol-4-yl]-1,3-thiazol-4-yl]hepta-2,6-dienamide
|
| 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 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)
|
| 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
|
|---|---|
| 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 | 2.0505 mL | 10.2526 mL | 20.5052 mL | |
| 5 mM | 0.4101 mL | 2.0505 mL | 4.1010 mL | |
| 10 mM | 0.2051 mL | 1.0253 mL | 2.0505 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
