| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
| Targets |
The primary targets of ascomycin are FKBP12 (FK506-binding protein 12) and calcineurin. Ascomycin binds to FKBP12, and the complex then inhibits calcineurin, a calcium/calmodulin-dependent serine/threonine phosphatase. Inhibition of calcineurin prevents the dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T-cells), thereby inhibiting T-cell activation and cytokine production. This mechanism is similar to that of tacrolimus (FK-506).
|
|---|---|
| ln Vitro |
In vitro, ascomycin is a potent immunosuppressant that binds to FKBP12 and inhibits calcineurin activity. It inhibits T-cell activation and cytokine production by preventing NFAT nuclear translocation. It has shown activity in various in vitro models of immune function. Ascomycin has also demonstrated activity against certain parasites and has been investigated for its potential in treating dermatological conditions such as atopic dermatitis. Its in vitro potency is comparable to that of tacrolimus.
|
| ln Vivo |
In vivo, ascomycin has immunosuppressive activity and has been investigated for topical use in dermatological conditions. It has been studied as a treatment for atopic dermatitis and other inflammatory skin diseases. Its systemic use is limited due to its immunosuppressive effects and potential for adverse events. Ascomycin has also been investigated for its antiparasitic activity, particularly against Plasmodium species (malaria) and other parasites.
|
| Enzyme Assay |
In vitro non-cellular binding assays for ascomycin typically involve: (1) prepare FKBP12 protein; (2) incubate FKBP12 with ascomycin at various concentrations; (3) measure binding affinity using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC); (4) assess competitive binding with FK-506 or other FKBP12 ligands; (5) measure calcineurin inhibition by evaluating its phosphatase activity using p-nitrophenyl phosphate or phosphopeptide substrates; and (6) determine IC₅₀ values for calcineurin inhibition.
|
| Cell Assay |
In vitro cell-based assays for ascomycin typically involve: (1) culture T cells (e.g., Jurkat cells or primary human T cells) in appropriate medium; (2) stimulate T cells with anti-CD3/CD28 antibodies or PMA/ionomycin; (3) treat cells with ascomycin at various concentrations (0.1-100 nM); (4) measure cytokine production (IL-2, IFN-γ) by ELISA or intracellular flow cytometry; (5) assess T-cell proliferation by [³H]-thymidine incorporation or CFSE dilution; (6) evaluate NFAT nuclear translocation by immunofluorescence or Western blot; and (7) calculate IC₅₀ values for inhibition of T-cell activation.
|
| Animal Protocol |
In vivo animal experiments with ascomycin typically involve models of transplantation or autoimmune disease. A common protocol is: (1) administer ascomycin to mice or rats via oral gavage, intraperitoneal injection, or topical application at doses of 1-50 mg/kg; (2) in transplant models, perform skin or organ transplantation and monitor graft survival; (3) in autoimmune models (e.g., contact hypersensitivity, experimental autoimmune encephalomyelitis), assess disease severity; (4) collect blood and tissue samples for immunological analysis; (5) measure cytokine levels and lymphocyte subsets; and (6) evaluate histopathology of target tissues.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of ascomycin: It has a molecular weight of 792 and is a lipophilic macrolide. It has a boiling point of 868.3°C and a density of 1.2 g/cm³. As a topical agent, ascomycin has limited systemic absorption. When administered systemically, it is metabolized by CYP3A4 and has a half-life of several hours. Its pharmacokinetic profile is similar to that of tacrolimus. It is highly protein-bound and distributed primarily in the blood and tissues.
|
| Toxicity/Toxicokinetics |
The toxicity profile of ascomycin is similar to that of other calcineurin inhibitors. Common adverse effects include nephrotoxicity, neurotoxicity, gastrointestinal disturbances, and increased risk of infections. Topical use may cause local irritation and burning sensation. Systemic use is limited due to the potential for serious adverse effects. The compound is for research use only and is not approved for human therapeutic use in many jurisdictions.
|
| References |
[1]. https://pubchem.ncbi.nlm.nih.gov/compound/6507974
|
| Additional Infomation |
Ascomycin is a macrolide antibiotic produced by the fermentation of *Streptomyces hygroscopicus*, and possesses potent immunosuppressive activity. It can be used as an immunosuppressant, antifungal agent, and bacterial metabolite. It is a macrolide antibiotic, and also an ether, secondary alcohol, and lactone compound. Ascomycin has been reported to exist in *Streptomyces ascomycinicus*, *Streptomyces hygroscopicus*, and *Streptomyces clavuligerus*, and relevant data are available. Derived from *Streptomyces hygroscopicus*; structure see first source.
This compound is also known as longchuanmycin and is produced by Streptomyces hygroscopicus. It is an analog of FK-506 (tacrolimus) and is a potent immunosuppressant. It binds to FKBP12 and inhibits calcineurin and NFAT activation. The molecular formula is C₄₃H₆₉NO₁₂ and the molecular weight is 792. This product is not a drug and has no clinical trial or regulatory approval status for systemic use. |
| Molecular Formula |
C43H69NO12
|
|---|---|
| Molecular Weight |
792
|
| Exact Mass |
791.482
|
| CAS # |
11011-38-4
|
| PubChem CID |
5282071
|
| Appearance |
White to off-white solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
868.3±75.0 °C at 760 mmHg
|
| Melting Point |
156 -161ºC
|
| Flash Point |
478.9±37.1 °C
|
| Vapour Pressure |
0.0±0.6 mmHg at 25°C
|
| Index of Refraction |
1.546
|
| LogP |
3.81
|
| Hydrogen Bond Donor Count |
3
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
56
|
| Complexity |
1430
|
| Defined Atom Stereocenter Count |
14
|
| SMILES |
CCC1C=C(CC(CC(C2C(CC(C(O2)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C(CC1=O)O)C)C(=CC4CCC(C(C4)OC)O)C)O)C)OC)OC)C)C
|
| InChi Key |
ZDQSOHOQTUFQEM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C43H69NO12/c1-10-30-18-24(2)17-25(3)19-36(53-8)39-37(54-9)21-27(5)43(51,56-39)40(48)41(49)44-16-12-11-13-31(44)42(50)55-38(28(6)33(46)23-34(30)47)26(4)20-29-14-15-32(45)35(22-29)52-7/h18,20,25,27-33,35-39,45-46,51H,10-17,19,21-23H2,1-9H3
|
| Chemical Name |
17-ethyl-1,14-dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone
|
| Synonyms |
Ascomycin, Streptomyces hygroscopicus; 11011-38-4; (18E)-17-ethyl-1,14-dihydroxy-12-[(E)-1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone; SCHEMBL10262882; HMS5085L14;
|
| 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 |
| 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 | 1.2626 mL | 6.3131 mL | 12.6263 mL | |
| 5 mM | 0.2525 mL | 1.2626 mL | 2.5253 mL | |
| 10 mM | 0.1263 mL | 0.6313 mL | 1.2626 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
