| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 100mg | |||
| 250mg | |||
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| Targets |
Monovalent cations (K+, NH4+); also inhibits P-glycoprotein (P-gp), adenine nucleotide translocase (ANT) isoforms ANT1-4, and HSP60 surface expression.
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| ln Vitro |
Nonactin acts as an ionophore for monovalent cations, including K+ and NH4+, with a selectivity order of K+ = NH4+ > Na+ > Mg2+ > Li+ >> Ca2+. It induces cation transport across artificial membranes. Nonactin inhibits P-glycoprotein-mediated efflux of chemotherapeutic agents in multiple-drug resistant cancer cells with an IC50 of 0.4 μM for 50% inhibition of efflux. It is an oxidative phosphorylation (OXPHOS) uncoupler. Nonactin inhibits recombinant human adenine nucleotide translocase (ANT) isoforms ANT1-4 with IC50 values of 4.4, 3.3, 4.7, and 3.3 μM, respectively. Nonactin selectively causes apoptosis in cells containing mutant β-catenin and inhibits the surface expression of endogenous HSP60. The compound exhibits antibacterial, insecticidal, and acaricidal properties.
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| ln Vivo |
In vivo, Nonactin has antitumor activity. It induces apoptosis in beta-catenin mutant tumor cells. The compound exhibits antibacterial, insecticidal, and acaricidal properties. Nonactin has been used in agriculture under the trade name POLYNACTIN. Specific dosing regimens and detailed efficacy data are available in the primary literature. As an OXPHOS uncoupler, nonactin affects mitochondrial function and energy metabolism in vivo.
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| Enzyme Assay |
Ionophore activity is assessed using artificial membrane assays (e.g., planar lipid bilayers, liposome-based assays) or by measuring ion transport using ion-selective electrodes. P-glycoprotein inhibition is evaluated using efflux assays with fluorescent substrates (e.g., rhodamine 123, calcein-AM) in MDR cancer cell lines. The concentration that must be used to inhibit 50% of the efflux is determined. OXPHOS uncoupling is measured by assessing mitochondrial oxygen consumption using oxygen electrode or Seahorse metabolic analyzers. ANT inhibition is measured using in vitro assays with recombinant human ANT isoforms. Apoptosis induction is evaluated in cell-based assays.
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| Cell Assay |
Cellular activity is evaluated in cancer cell lines, including multi-drug resistant cells (e.g., K562 drug-resistant cells) and cells with mutant β-catenin. Cells are treated with Nonactin at various concentrations (typically 0.01-100 μM) for 24-72 hours. Cell viability is measured by MTT, MTS, or CellTiter-Glo assays. P-glycoprotein-mediated efflux is assessed by measuring the accumulation of fluorescent substrates (e.g., rhodamine 123, calcein-AM) by flow cytometry or fluorescence plate reader. Apoptosis is measured by caspase-3/7 activation assays, Annexin V/PI staining, or PARP cleavage by Western blot. HSP60 surface expression is assessed by flow cytometry using anti-HSP60 antibodies. Mitochondrial function is assessed by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using Seahorse analyzers.
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| Animal Protocol |
In vivo efficacy is studied in mouse xenograft models of cancer, particularly those with mutant β-catenin. Nonactin is administered via various routes (oral, intraperitoneal, intravenous) at doses determined from preliminary pharmacokinetic and tolerability studies. Tumor growth is measured by caliper twice weekly and tumor volume is calculated. At study termination, tumors are excised and weighed. Tumor tissues are analyzed for apoptosis (TUNEL, caspase-3 activation), β-catenin signaling (Western blot, immunohistochemistry), and HSP60 expression. Pharmacodynamic markers include mitochondrial function and OXPHOS status in tumor tissue. The compound has also been studied in agricultural applications under the name POLYNACTIN.
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| ADME/Pharmacokinetics |
Nonactin has a molecular formula of C40H64O12 and a molecular weight of 736.94 g/mol. CAS Number: 6833-84-7. Purity: typically ≥95% by HPLC. Target: Metabolic Enzyme/Protease. The compound is an antibiotic ionophore. Nonactin is soluble in ethanol, methanol, DMF, or DMSO, but has poor water solubility. It is a natural mixture of macrotetrolides. The compound complexes and transports monovalent cations with affinities in the order Li+ > Na+ > Cs+ > K+ > Rb+ > NH4+. Detailed pharmacokinetic parameters are available from the primary literature.
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| Toxicity/Toxicokinetics |
Safety data for Nonactin indicate it is a research compound for laboratory use only. As an ionophore and OXPHOS uncoupler, it may have mitochondrial toxicity and affect cellular energy metabolism. The compound should be handled with appropriate safety precautions in a biological safety cabinet. Avoid inhalation, ingestion, and skin contact. Use personal protective equipment (gloves, lab coat, safety goggles) and adequate ventilation. The compound is for research use only and not for human therapeutic applications without appropriate regulatory approval. Consult the material safety data sheet (MSDS) for detailed safety information, including potential hazards and disposal considerations.
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| References |
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| Additional Infomation |
Nonactin is a macrocyclic tetralactone. It has been reported that Nonactin is found in both Streptomyces coccidioides and Streptomyces griseus, and relevant data exists.
Nonactin is a research tool compound for studying ion transport, P-glycoprotein function, mitochondrial biology, and apoptosis. It is not approved for clinical use. The compound has been investigated for anti-tumor applications, particularly in cancers with mutant β-catenin. Nonactin is also known as Ammonium Ionophore I. It is the parent compound of the macrotetrolides, a group of ionophore antibiotics produced by Streptomyces species. Nonactin has been used in agriculture under the trade name POLYNACTIN. The compound's ability to inhibit P-glycoprotein-mediated efflux makes it a valuable tool for studying multidrug resistance mechanisms and for potentially enhancing the efficacy of chemotherapeutic agents. |
| Molecular Formula |
C40H64O12
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|---|---|
| Molecular Weight |
736.94
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| Exact Mass |
736.44
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| CAS # |
6833-84-7
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| PubChem CID |
72519
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| Appearance |
White to off-white solid powder
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| Density |
1.041 g/cm3
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| Boiling Point |
890.6ºC at 760 mmHg
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| Melting Point |
147-148°
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| Flash Point |
352.7ºC
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| Index of Refraction |
1.452
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| LogP |
6.022
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
52
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| Complexity |
1040
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| Defined Atom Stereocenter Count |
16
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| SMILES |
C[C@@H]1C[C@H]2CC[C@H](O2)[C@@H](C(=O)O[C@H](C[C@@H]3CC[C@@H](O3)[C@H](C(=O)O[C@@H](C[C@H]4CC[C@H](O4)[C@@H](C(=O)O[C@H](C[C@@H]5CC[C@@H](O5)[C@H](C(=O)O1)C)C)C)C)C)C)C
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| InChi Key |
RMIXHJPMNBXMBU-QIIXEHPYSA-N
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| InChi Code |
InChI=1S/C40H64O12/c1-21-17-29-9-13-34(49-29)26(6)38(42)46-23(3)19-31-11-15-36(51-31)28(8)40(44)48-24(4)20-32-12-16-35(52-32)27(7)39(43)47-22(2)18-30-10-14-33(50-30)25(5)37(41)45-21/h21-36H,9-20H2,1-8H3/t21-,22+,23+,24-,25-,26+,27+,28-,29-,30+,31+,32-,33-,34+,35+,36-
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| Chemical Name |
(1R,2R,5R,7R,10S,11S,14S,16S,19R,20R,23R,25R,28S,29S,32S,34S)-2,5,11,14,20,23,29,32-octamethyl-4,13,22,31,37,38,39,40-octaoxapentacyclo[32.2.1.17,10.116,19.125,28]tetracontane-3,12,21,30-tetrone
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| Synonyms |
A5584; A-5584; Nonactin
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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) |
DMF : 50 mg/mL (~67.85 mM)
DMSO : ~6.67 mg/mL (~9.05 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 | 1.3570 mL | 6.7848 mL | 13.5696 mL | |
| 5 mM | 0.2714 mL | 1.3570 mL | 2.7139 mL | |
| 10 mM | 0.1357 mL | 0.6785 mL | 1.3570 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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