| Size | Price | Stock | Qty |
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| Targets |
Manumycin A has multiple targets, which contribute to its diverse biological activities. Its primary known target is the enzyme farnesyltransferase, which it inhibits. By inhibiting farnesyltransferase, it prevents the prenylation of proteins, including Ras, which is crucial for their proper cellular localization and function. It also targets and inhibits the Ras/Raf/ERK1/2 signaling pathway. Furthermore, it is an inhibitor of neutral sphingomyelinase (nSMase) and targets protein phosphatase 1 alpha (PP1alpha).
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| ln Vitro |
In vitro, Manumycin A exhibits multiple activities. It inhibits Ras farnesyltransferase, impacting cellular pathways involving prenylated proteins. It suppresses exosome biogenesis and secretion via targeted inhibition of Ras/Raf/ERK1/2 signaling. It also blocks insulin-induced MAP kinase activation in rat cardiac myocytes (19 µM). Its inhibition of nSMase (EC50=0.25 µM) is another key in vitro activity.
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| ln Vivo |
In vivo, Manumycin A has been shown to exert anti-tumor effects. It causes apoptosis and has been studied for its potential in cancer therapy. It has also been studied for its ability to correct aberrant splicing of the muscle chloride channel Clcn1 in a mouse model of myotonic dystrophy type 1 (DM1). These in vivo activities are based on its multiple mechanisms of action. However, specific in vivo data is not detailed in the available literature.
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| Enzyme Assay |
Cell-free assays for Manumycin A are performed to measure its inhibition of its various targets. For farnesyltransferase inhibition, a common assay involves incubating the recombinant enzyme with its substrate (a farnesylated peptide) and farnesyl pyrophosphate in the presence of varying concentrations of Manumycin A. The incorporation of the farnesyl group into the substrate is measured. For nSMase inhibition, the enzyme is incubated with its substrate, sphingomyelin, and the production of ceramide is measured. These assays allow the direct quantification of its inhibitory activity.
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| Cell Assay |
In vitro cell-based assays for Manumycin A are performed to study its effects on cancer cells and other cell types. Cells are treated with the compound, and its effects on cell viability, proliferation, and apoptosis are assessed using standard assays like MTT, Annexin V staining, and caspase activity assays. Its effect on exosome secretion can be measured by quantifying the amount of exosomes released into the culture medium. Its effect on MAP kinase signaling can be assessed by Western blotting for phosphorylated ERK1/2.
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| Animal Protocol |
In vivo animal experiments for Manumycin A would involve models of cancer or other diseases. For cancer studies, xenograft models using immunodeficient mice implanted with human tumor cells could be used. The compound would be administered, and tumor growth would be monitored. For studies on myotonic dystrophy, a mouse model of the disease could be used, and the effect of the compound on muscle chloride channel splicing would be assessed. Specific protocols are not detailed in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for Manumycin A is not provided in the available literature. As a natural product, its properties, such as oral bioavailability and half-life, would be important for its development. For storage, the compound is typically kept as a powder.
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| Toxicity/Toxicokinetics |
Toxicological data for Manumycin A is not available in the public literature. As a research compound, its safety profile would be a critical factor in its development. However, no specific LD50, organ toxicity, or genotoxicity data are reported. Its use is strictly for research purposes, and it is not intended for human therapeutic use.
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| References |
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| Additional Infomation |
Manumycin A is a polyketide compound with the molecular formula C31H38N2O7, initially isolated from Streptomyces parvulus as a result of random screening for farnesyltransferase (FTase) inhibitors. It is a natural product with anticancer and antibacterial activities. It functions as an EC 1.8.1.9 (thioredoxin reductase) inhibitor, an EC 2.5.1.58 (protein farnesyltransferase) inhibitor, an antitumor agent, an apoptosis inducer, an antibacterial agent, a bacterial metabolite, an anti-atherosclerotic agent, and a marine metabolite. It is a polyketide compound, an enamide, an epoxide, an organic heterobicyclic compound, a secondary carboxamide, and a tertiary alcohol. Manumycin A has been reported to exist in Streptomyces, Streptomyces griseoaurantiacus, and Streptomyces parvulus, and relevant data are available for reference.
Manumycin A is a research-grade natural product used as a tool to study various biological processes, including protein prenylation, exosome biogenesis, and sphingolipid metabolism. Its multiple targets make it a valuable compound for studying the interplay between these pathways. It has been studied for its potential anti-cancer and anti-inflammatory activities. It has not been approved for clinical use. All information is for research reference and not for diagnostic or clinical use. |
| Molecular Formula |
C31H38N2O7
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|---|---|
| Molecular Weight |
550.64262
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| Exact Mass |
550.267
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| CAS # |
52665-74-4
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| PubChem CID |
6438330
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| Appearance |
Yellow to orange solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
863.6±65.0 °C at 760 mmHg
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| Flash Point |
476.1±34.3 °C
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| Vapour Pressure |
0.0±0.6 mmHg at 25°C
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| Index of Refraction |
1.605
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| LogP |
3.04
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
40
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| Complexity |
1260
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CCCC[C@@H](C)/C=C(\C)/C=C(\C)/C(=O)NC1=C[C@]([C@H]2[C@@H](C1=O)O2)(/C=C/C=C/C=C/C(=O)NC3=C(CCC3=O)O)O
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| InChi Key |
TWWQHCKLTXDWBD-MVTGTTCWSA-N
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| InChi Code |
InChI=1S/C31H38N2O7/c1-5-6-11-19(2)16-20(3)17-21(4)30(38)32-22-18-31(39,29-28(40-29)27(22)37)15-10-8-7-9-12-25(36)33-26-23(34)13-14-24(26)35/h7-10,12,15-19,28-29,34,39H,5-6,11,13-14H2,1-4H3,(H,32,38)(H,33,36)/b8-7+,12-9+,15-10+,20-16+,21-17+/t19-,28-,29-,31+/m1/s1
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| Chemical Name |
(2E,4E,6R)-N-[(1S,5S,6R)-5-hydroxy-5-[(1E,3E,5E)-7-[(2-hydroxy-5-oxocyclopenten-1-yl)amino]-7-oxohepta-1,3,5-trienyl]-2-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]-2,4,6-trimethyldeca-2,4-dienamide
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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) |
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 | 1.8161 mL | 9.0803 mL | 18.1607 mL | |
| 5 mM | 0.3632 mL | 1.8161 mL | 3.6321 mL | |
| 10 mM | 0.1816 mL | 0.9080 mL | 1.8161 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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