| Size | Price | Stock | Qty |
|---|---|---|---|
| 1g |
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| Other Sizes |
Purity: ≥550ug/mg(dried basis)
Apramycin (also known as Ai3-29795; Nebramycin II) is a broad spectrum and aminoglycoside class of antibiotic, which binds to the deep groove of the RNA. Apramycin consumption at farm level is most probably driving the increasing occurrence of apramycin/gentamicin cross-resistant [aac(3)-IV positive] E. coli in diseased pigs and healthy finishers at slaughter. Apramycin inhibits A. pleuropneumoniae FMV 87-682 with MIC50 of 8 mg/L. Apramycin (1/4 MIC) in the medium decreases the rate of growth of the bacterial strains tested, and causes the postantibiotic effect (PAE) up to 5 hours.
| Targets |
Aminoglycoside
Apramycin Sulfate (Nebramycin II) targets the bacterial 30S ribosomal subunit, inhibiting bacterial protein synthesis [1,2] |
|---|---|
| ln Vitro |
Apramycin consumption at farm level is most probably driving the increasing occurrence of apramycin/gentamicin cross-resistant [aac(3)-IV positive] E. coli in diseased pigs and healthy finishers at slaughter. Apramycin inhibits A. pleuropneumoniae FMV 87-682 with MIC50 of 8 mg/L. Apramycin (1/4 MIC) in the medium decreases the rate of growth of the bacterial strains tested, and causes the postantibiotic effect (PAE) up to 5 hours. Apramycin significantly reduces the haemolytic activity of A. pleuropneumoniae and affects the capsular material production of this isolate and of one isolate of P. multocida (type A). Apramycin induces translation errors, as assayed by incorporation of leucine, isoleucine and serine, although this effect occurs only to a limited extent, in cell-free systems from Escherichia coli programmed with poly(U). Apramycin inhibits the translocation step of protein synthesis both in vivo, in protoplasts of Bacillus megaterium, and in vitro, in cell-free systems from E. coli.
Against Mycobacterium tuberculosis (including isoniazid-resistant strains), Apramycin Sulfate (Nebramycin II) exhibited antibacterial activity with minimum inhibitory concentrations (MICs) of 2–8 μg/mL (susceptible strains) and 4–16 μg/mL (isoniazid-resistant strains). It inhibited bacterial growth by ~70% at 8 μg/mL for susceptible strains [1] - For Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhimurium), Apramycin Sulfate (Nebramycin II) showed potent activity with MICs of 0.5–4 μg/mL (E. coli), 1–8 μg/mL (K. pneumoniae), 2–16 μg/mL (P. aeruginosa), and 0.25–2 μg/mL (S. typhimurium). It completely suppressed bacterial colony formation at 8 μg/mL for E. coli and S. typhimurium [2] - Apramycin Sulfate (Nebramycin II) (2–16 μg/mL) inhibited bacterial protein synthesis in E. coli cell-free systems: at 8 μg/mL, [3H]-leucine incorporation into proteins was reduced by ~85% compared to control [2] |
| ln Vivo |
Apramycin (225 mg/L) totally suppresses mortality and significantly reduces Salmonella excretion in comparison with non-treated chicks.
In Swiss albino mice with intraperitoneal E. coli infection (1×108 CFU/mouse), subcutaneous administration of Apramycin Sulfate (Nebramycin II) (10, 20, 40 mg/kg) twice daily for 3 days dose-dependently improved survival rate: 40 mg/kg group had a 90% survival rate vs. 20% in vehicle control. Bacterial load in peritoneal fluid was reduced by ~95% at 40 mg/kg [2] - In mice with M. tuberculosis aerosol infection, intramuscular injection of Apramycin Sulfate (Nebramycin II) (50 mg/kg/day for 4 weeks) reduced lung bacterial colony-forming units (CFU) by ~68% compared to untreated mice. It also attenuated lung inflammation, with reduced granuloma size and neutrophil infiltration [1] |
| Enzyme Assay |
Bacterial ribosomal binding assay: Recombinant bacterial 30S ribosomal subunits were incubated with Apramycin Sulfate (Nebramycin II) (0.5–32 μg/mL) in binding buffer at 37°C for 1 hour. A fluorescently labeled mRNA mimic was added, and fluorescence polarization was measured to assess the binding affinity of the drug to the 30S subunit. The inhibition of mRNA-ribosome interaction was quantified by comparing fluorescence signals of drug-treated and control groups [2]
- Bacterial protein synthesis inhibition assay: E. coli cell-free extracts (containing ribosomes, mRNA, tRNA, and enzymes) were mixed with Apramycin Sulfate (Nebramycin II) (2–16 μg/mL) and [3H]-leucine. The mixture was incubated at 37°C for 60 minutes, and the reaction was terminated by adding trichloroacetic acid. Radioactivity of precipitated proteins was measured by liquid scintillation counting to determine the inhibition rate of protein synthesis [2] |
| Cell Assay |
MIC determination assay: Bacterial strains (M. tuberculosis, E. coli, K. pneumoniae, etc.) were cultured to mid-log phase and adjusted to 1×105 CFU/mL. Apramycin Sulfate (Nebramycin II) was serially diluted (0.125–32 μg/mL) in Mueller-Hinton broth (for Gram-negative bacteria) or Middlebrook 7H9 broth (for M. tuberculosis) in 96-well plates. Bacterial suspensions were added, and plates were incubated at 37°C for 24 hours (Gram-negative bacteria) or 7 days (M. tuberculosis). MIC was defined as the lowest concentration inhibiting visible bacterial growth [1,2]
- Bacterial colony formation assay: E. coli or S. typhimurium were treated with Apramycin Sulfate (Nebramycin II) (2–16 μg/mL) for 2 hours, then serially diluted and plated on agar plates. Plates were incubated at 37°C for 24 hours, and colony numbers were counted to assess bacterial viability [2] |
| Animal Protocol |
225 mg/L
Chicks E. coli infection mouse model: 20–25 g Swiss albino mice were intraperitoneally injected with E. coli suspension (1×108 CFU/mouse) to induce systemic infection. Apramycin Sulfate (Nebramycin II) was dissolved in normal saline and administered subcutaneously at 10, 20, or 40 mg/kg twice daily (12-hour interval) for 3 days. Control mice received normal saline. Survival rate was recorded daily for 7 days. At 48 hours post-infection, peritoneal fluid was collected for bacterial load quantification (CFU/mL) [2] - M. tuberculosis aerosol infection mouse model: 6–8-week-old C57BL/6 mice were exposed to M. tuberculosis aerosol (1×105 CFU/mouse) to establish pulmonary infection. Apramycin Sulfate (Nebramycin II) was dissolved in normal saline and administered intramuscularly at 50 mg/kg/day for 4 weeks. Control mice received normal saline. Mice were sacrificed at the end of treatment, and lung tissues were homogenized for CFU counting and histological analysis [1] |
| ADME/Pharmacokinetics |
After subcutaneous injection of apramycin sulfate (nebramycin II) (20 mg/kg) into mice, the peak plasma concentration (Cmax) at 1 hour was 18 μg/mL (Tmax), and the plasma elimination half-life (t1/2) was approximately 2.5 hours [2]. The drug is widely distributed in tissues, with the highest concentrations in the kidneys (42 μg/g) and liver (12 μg/g) 2 hours after administration, while the concentration in brain tissue was lower (0.8 μg/g), which is due to its poor blood-brain barrier penetration [2]. Apramycin sulfate (nebramycin II) is mainly excreted unchanged in the urine: approximately 85% of the administered dose is excreted in the urine within 24 hours [2].
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| Toxicity/Toxicokinetics |
In vitro toxicity: Apramycin sulfate (nabramycin II) (0.5–32 μg/mL) showed no cytotoxicity to normal human fibroblasts or epithelial cells, and cell viability remained above 90% at all tested concentrations [2]. In vivo toxicity: Subcutaneous or intramuscular injection of apramycin sulfate (nabramycin II) (10–50 mg/kg/day for 4 weeks) in mice did not cause significant changes in body weight or obvious toxic symptoms (e.g., somnolence, loss of appetite). Serum creatinine and urea nitrogen levels were slightly elevated (approximately 15%) at a dose of 50 mg/kg/day, but remained within the normal range [1,2].
|
| References | |
| Additional Infomation |
Apramycin sulfate is a glycoside and aminocyclic alcohol antibiotic.
Apramycin sulfate (nabramycin II) is an aminoglycoside antibiotic derived from Streptomyces tenebrarius, exhibiting broad-spectrum antibacterial activity against Gram-negative bacteria and Mycobacterium tuberculosis [1,2]. - Its core mechanism of action is binding to the 30S ribosomal subunit of bacteria, interfering with the binding of mRNA to the ribosome, leading to mRNA misreading, thereby inhibiting bacterial protein synthesis and ultimately causing bacterial death [1,2]. - It is also active against isoniazid-resistant Mycobacterium tuberculosis strains, making it a potential candidate drug for treating drug-resistant tuberculosis [1]. - Apramycin sulfate (nabramycin II) is primarily used to treat severe Gram-negative bacterial infections and tuberculosis, especially severe tuberculosis. In cases of resistance [1,2] |
| Molecular Formula |
C21H43N5O15S
|
|---|---|
| Molecular Weight |
637.66
|
| Exact Mass |
637.247
|
| Elemental Analysis |
C, 39.56; H, 6.80; N, 10.98; O, 37.64; S, 5.03
|
| CAS # |
65710-07-8
|
| Related CAS # |
65710-07-8 (sulfate);37321-09-8;
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| PubChem CID |
3081544
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| Appearance |
White to yellow solid powder
|
| Density |
1.56
|
| Boiling Point |
949.8ºC at 760 mmHg
|
| Melting Point |
>168ºC (dec.)
|
| Flash Point |
528.2ºC
|
| LogP |
3.825
|
| Hydrogen Bond Donor Count |
13
|
| Hydrogen Bond Acceptor Count |
20
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
42
|
| Complexity |
841
|
| Defined Atom Stereocenter Count |
17
|
| SMILES |
S(=O)(=O)(O[H])O[H].O1[C@@]([H])([C@@]([H])(C([H])([H])[C@@]2([H])[C@@]1([H])[C@@]([H])([C@@]([H])([C@@]([H])(O[C@]1([H])[C@@]([H])([C@]([H])([C@@]([H])([C@@]([H])(C([H])([H])O[H])O1)N([H])[H])O[H])O[H])O2)N([H])C([H])([H])[H])O[H])N([H])[H])O[C@@]1([H])[C@@]([H])([C@]([H])([C@@]([H])(C([H])([H])[C@]1([H])N([H])[H])N([H])[H])O[H])O[H]
|
| InChi Key |
WGLYHYWDYPSNPF-RQFIXDHTSA-N
|
| InChi Code |
InChI=1S/C21H41N5O11.H2O4S/c1-26-11-14(30)18-8(33-20(11)37-21-16(32)13(29)10(25)9(4-27)34-21)3-7(24)19(36-18)35-17-6(23)2-5(22)12(28)15(17)31;1-5(2,3)4/h5-21,26-32H,2-4,22-25H2,1H3;(H2,1,2,3,4)/t5-,6+,7-,8+,9-,10-,11+,12+,13+,14-,15-,16-,17-,18+,19+,20-,21-;/m1./s1
|
| Chemical Name |
(2R,3R,4S,5S,6S)-2-[[(2R,3S,4R,4aR,6S,7R,8aS)-7-amino-6-[(1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxycyclohexyl]oxy-4-hydroxy-3-(methylamino)-2,3,4,4a,6,7,8,8a-octahydropyrano[3,2-b]pyran-2-yl]oxy]-5-amino-6-(hydroxymethyl)oxane-3,4-diol sulfuric acid
|
| Synonyms |
Apramycin (sulfate); Apramycin sulphate; Apramycin Sulfate; Apramycin-Sulfate; ApramycinSulfate
|
| HS Tariff Code |
2934.99.03.00
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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)
|
| Solubility (In Vitro) |
Water : 100~200 mg/mL(313.65 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (156.82 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
Solubility in Formulation 2: PBS : 100 mg/mL (156.82 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5682 mL | 7.8412 mL | 15.6823 mL | |
| 5 mM | 0.3136 mL | 1.5682 mL | 3.1365 mL | |
| 10 mM | 0.1568 mL | 0.7841 mL | 1.5682 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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