| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
Ergosterol (fungal cell membrane). Amphotericin B methyl ester binds to ergosterol, the primary sterol in fungal cell membranes, forming transmembrane channels that disrupt membrane integrity. This leads to leakage of intracellular ions and macromolecules, resulting in fungal cell death. The methyl ester retains the same basic mechanism of action as the parent polyene antibiotic.
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| ln Vitro |
Amphotericin B methyl ester prevents the formation of HIV-1 particles while having no discernible impact on the plasma membrane binding, lipid raft association, or multimerization of Gag[1].
AME has significant antifungal activity, although its potency is generally slightly lower than that of amphotericin B. Against a panel of 465 clinical isolates of Candida albicans, AME possesses comparable activity to AMB against half of the strains. The minimal fungicidal concentration (MFC) for yeast-like organisms like Sporothrix schenckii is 5-10 microg/mL. |
| ln Vivo |
In murine models of systemic fungal infections (histoplasmosis, blastomycosis, cryptococcosis, candidosis), daily intraperitoneal therapy with AME improved 21-day survival and reduced persistence of organisms in internal organs, demonstrating in vivo efficacy. In a rabbit eye model of deep stromal yeast infection, topical 1% AME was highly efficacious when the corneal epithelium was absent.
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| Enzyme Assay |
Cell-free enzyme assays are not applicable. Instead, ergosterol binding affinity is assessed by measuring the decrease in the compound's UV-Vis absorbance spectrum upon interaction with ergosterol-containing liposomes. AME (10-50 microM) is incubated with ergosterol liposomes in phosphate-buffered saline (PBS, pH 7.4) for 15-30 min at 25degC, and the spectral shift is recorded.
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| Cell Assay |
Candida albicans ATCC 10231 cells are cultured in RPMI-1640 medium (buffered to pH 7.0 with MOPS) at 35degC for 24 h. Cells are diluted to 1-5 × 103 CFU/mL and seeded in 96-well plates with varying concentrations of AME (0.1-100 microg/mL). Plates are incubated for 24-48 h, and fungal growth is measured by absorbance at 530 nm. The MIC is defined as the lowest concentration producing ≥80% growth inhibition compared to untreated controls.
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| Animal Protocol |
Female BALB/c mice (6-8 weeks, 18-22 g) are infected intravenously with 5 × 10⁵ CFU of Candida albicans or Cryptococcus neoformans. One hour post-infection, AME is administered intraperitoneally at 0.5-5 mg/kg daily for 10-14 days. Survival is recorded daily for up to 21 days. On day 21, surviving mice are euthanized, kidneys/lungs are homogenized and plated on Sabouraud dextrose agar for colony counting to quantify fungal burden (CFU/organ).
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| ADME/Pharmacokinetics |
AME is a basic compound with excellent water solubility (especially as the hydrochloride salt), a key improvement over amphotericin B. Like amphotericin B, it is primarily distributed to the liver, spleen, and lungs. The methyl ester derivative is likely metabolized similarly to the parent drug (via oxidation and glucuronidation). Detailed human PK profiles are limited, as AME did not reach clinical approval.
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| Toxicity/Toxicokinetics |
Hepatotoxicity
Up to 20% of patients treated with amphotericin B may experience mild and transient elevations in liver enzymes. Clinically significant hepatotoxicity is rare, but several confirmed cases have been reported. Liver injury can occur as early as 4 to 14 days after the start of treatment, usually manifesting as hepatocellular or mixed elevations in liver enzymes. Most patients are asymptomatic or have jaundice. Recovery is rapid after discontinuation of the drug. Additionally, there have been reports of isolated but severe bilirubinemia, primarily manifested as elevated direct (conjugated) bilirubin, occurring within days of starting amphotericin B treatment. These patients present with gross jaundice but without systemic symptoms, and serum ALT or alkaline phosphatase levels show only slight or no elevation, with no obvious signs of liver injury. Finally, there have been rare reports of acute cholestatic hepatitis with jaundice in patients treated with amphotericin B, but these patients are usually critically ill and have been exposed to multiple potentially hepatotoxic drugs, thus the pathogenicity of amphotericin B is relatively low. Probability Score: C (Possibly a cause of clinically significant liver injury). The major dose-limiting toxicity of amphotericin B is nephrotoxicity. AME was developed to reduce this toxicity, but clinical trials revealed delayed neurotoxicity (e.g., leukoencephalopathy) in some patients at high cumulative doses, leading to discontinuation of its clinical development. In vitro, AME inhibits HIV-1 particle production. |
| References |
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| Additional Infomation |
Amphotericin B methyl ester is a methyl ester derivative of amphotericin B. It possesses antifungal, anti-infective, and metabolic activities. It is a macrolide antibiotic, belonging to the monosaccharide derivative and methyl ester class of compounds. Its function is related to that of amphotericin B. Amphotericin B is a broad-spectrum antifungal drug with antibacterial activity against a variety of fungi. Amphotericin B usually causes mild to moderate elevation of serum transaminases and may cause hyperbilirubinemia, but acute, clinically significant drug-induced liver injury caused by amphotericin B treatment is extremely rare.
Amphotericin B was FDA-approved in 1966 for severe systemic fungal infections. AME is now a research chemical used as a water-soluble, investigational antifungal agent and as a tool to study the mechanisms of polyene antifungal activity and toxicity, particularly the dissociation of antifungal efficacy from nephrotoxicity and neurotoxicity. |
| Molecular Formula |
C48H75NO17
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|---|---|
| Molecular Weight |
938.105600000001
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| Exact Mass |
937.503
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| Elemental Analysis |
C, 61.46; H, 8.06; N, 1.49; O, 28.99
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| CAS # |
36148-89-7
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| Related CAS # |
Amphotericin B methyl ester hydrochloride;35375-29-2
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| PubChem CID |
11968030
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
1102.6±65.0 °C at 760 mmHg
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| Flash Point |
620.6±34.3 °C
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| Vapour Pressure |
0.0±0.6 mmHg at 25°C
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| Index of Refraction |
1.602
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| LogP |
1.63
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| Hydrogen Bond Donor Count |
11
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| Hydrogen Bond Acceptor Count |
18
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
66
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| Complexity |
1680
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| Defined Atom Stereocenter Count |
19
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| SMILES |
C1=CC=CC=CC=C[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N)[C@@H]2O)C[C@H]2[C@@H]([C@H](C[C@@](O2)(O)C[C@@H](O)C[C@@H](O)[C@H](O)CC[C@@H](O)C[C@@H](O)CC(=O)O[C@@H](C)[C@H](C)[C@H](O)[C@@H](C)C=CC=CC=C1)O)C(OC)=O |c:61,t:0,2,4,6,57,59,&1:8,10,12,14,16,18,21,22,23,25,29,32,34,38,41,47,49,51,53|
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| InChi Key |
UAZIZEMIKKIBCA-TYVGYKFWSA-N
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| InChi Code |
InChI=1S/C48H75NO17/c1-28-18-16-14-12-10-8-6-7-9-11-13-15-17-19-35(65-47-45(59)42(49)44(58)31(4)64-47)25-39-41(46(60)62-5)38(55)27-48(61,66-39)26-34(52)23-37(54)36(53)21-20-32(50)22-33(51)24-40(56)63-30(3)29(2)43(28)57/h6-19,28-39,41-45,47,50-55,57-59,61H,20-27,49H2,1-5H3/b7-6+,10-8+,11-9+,14-12+,15-13+,18-16+,19-17+/t28-,29-,30-,31+,32+,33+,34-,35-,36+,37+,38-,39-,41+,42-,43+,44+,45-,47-,48+/m0/s1
|
| Chemical Name |
methyl (1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-(((2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylate
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~53.30 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 | 1.0660 mL | 5.3299 mL | 10.6597 mL | |
| 5 mM | 0.2132 mL | 1.0660 mL | 2.1319 mL | |
| 10 mM | 0.1066 mL | 0.5330 mL | 1.0660 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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