| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
Josamycin HCl is a novel and potent macrolide antibiotic
Josamycin HCl is the hydrochloride salt form of josamycin, a 16-membered ring macrolide antibiotic produced by strains of Streptomyces narbonensis var. josamyceticus. This compound has the molecular formula C₄₂H₇₀ClNO₁₅ and a molecular weight of 864.46 g/mol. As the salt form of josamycin, Josamycin HCl exhibits improved water solubility and stability, and is widely used clinically for the treatment of respiratory tract infections and skin/soft tissue infections caused by susceptible bacteria.| Targets |
The primary target of Josamycin HCl is the 50S large subunit of the bacterial ribosome. By reversibly binding to the 50S subunit (with a dissociation constant Kd of 5.5 nM), josamycin blocks the elongation of nascent peptides through the ribosomal exit tunnel, thereby inhibiting bacterial protein synthesis. Compared to 14-membered ring macrolides, josamycin exhibits a significantly longer average residence time on the ribosome, approximately 3 hours. At saturating drug concentrations, josamycin completely shuts down the synthesis of full-length proteins.
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| ln Vitro |
In vitro studies demonstrate that josamycin exhibits good antibacterial activity against various Gram-positive cocci, including pneumococci, Streptococcus pyogenes, Staphylococcus aureus, and Staphylococcus epidermidis. Josamycin shows superior activity against enterococci compared to clindamycin. Against anaerobes, josamycin demonstrates potent in vitro activity against various anaerobes including Bacteroides fragilis. In cell-free translation systems, josamycin binds to the ribosome with a dissociation constant Kd of 5.5 nM and has an average residence time of 3 hours on the ribosome. Josamycin slows down the formation of the first peptide bond of a nascent peptide in an amino acid-dependent manner and completely inhibits the formation of the second or third peptide bond, depending on the peptide sequence.
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| ln Vivo |
In vivo studies confirm that josamycin exhibits significant efficacy in animal models. In rabbit models, following oral administration of 200 mg/kg josamycin, the drug is distributed in blood and tissues, with tissue levels generally significantly higher than blood levels. Tissue levels at 3 hours after dosing are somewhat higher than at 1 hour when blood levels are at their lowest, with lung levels being the highest among all tissues. The in vivo therapeutic effect of josamycin cannot be assessed solely by blood concentration and MIC, which differs from the conventional rules of antibiotic evaluation. Josamycin exerts bactericidal effects through inhibition of protein elongation and depletion of the intracellular pool of aminoacyl-tRNA due to peptidyl-tRNA shedding.
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| Enzyme Assay |
Cell-free Translation System Construction: Construct a cell-free mRNA translation system using purified components from E. coli, including 70S ribosomes, aminoacyl-tRNA synthetases, initiation factors, and elongation factors.
Ribosome Binding Assay: Pre-incubate varying concentrations of josamycin (e.g., 0.5-100 nM) with ribosomes for 10-30 minutes.
Peptide Synthesis Detection: Add radiolabeled amino acids (e.g., [³⁵S]-methionine) or polypeptide templates, incubate at 37°C, and detect radioactivity of newly synthesized peptide chains by scintillation counting.
Dissociation Kinetics Determination: Monitor the dissociation rate of the josamycin-ribosome complex using excess unlabeled drug or rapid dilution methods. Results show that josamycin has an average residence time of 3 hours on the ribosome.
Data Analysis: Calculate the dissociation constant (Kd = 5.5 nM) and binding occupancy of the drug with the ribosome.
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| Cell Assay |
Cell Culture: Isolate and purify human peripheral blood neutrophils from healthy volunteer blood by Ficoll-Hypaque density gradient centrifugation.
Drug Treatment: Pre-incubate adherent neutrophils with josamycin HCl (0.1-25 mg/L) for 30-60 minutes, with a vehicle control group.
Antibacterial Activity Assay: Add S. aureus (approximately 1-5×10⁶ CFU/mL) at a bacteria-to-cell ratio of approximately 10:1, and incubate at 37°C for 60-120 minutes.
Bacterial Killing Detection: Lyse neutrophils with saponin to release engulfed bacteria, plate on agar plates for colony counting, and calculate killing rates.
Data Analysis: Compare bacterial killing rates between treatment and control groups. Josamycin can be concentrated up to 20-fold in phagocytic cells.
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| Animal Protocol |
Animal Models: Use Japanese white rabbits to establish skin infection models by intradermal injection of Staphylococcus aureus.
Dosing Regimen: Administer josamycin HCl by oral gavage at a dose of 200 mg/kg body weight.
Sample Collection: Collect blood and tissue samples (including lung, liver, kidney, spleen, etc.) at 1 hour and 3 hours after administration.
Drug Concentration Detection: Detect drug concentrations in plasma and tissues using microbial agar diffusion assays.
Data Analysis: Compare blood concentration and tissue distribution characteristics at different time points. Results show that tissue levels at 3 hours after dosing are higher than at 1 hour, with lung levels being the highest among all tissues.
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| ADME/Pharmacokinetics |
Josamycin is rapidly absorbed after oral administration, reaching peak plasma concentrations approximately 1 hour after a 1 g oral dose in healthy volunteers. The plasma protein binding rate of this drug is approximately 15%, significantly lower than other macrolide antibiotics. Josamycin has a plasma half-life of 1-2 hours. This drug exhibits high accumulation in lung tissue, with lung tissue concentrations 2-3 times higher than plasma concentrations. Josamycin has high lipophilicity and good tissue penetration, achieving high concentrations in bronchial secretions, prostatic tissue, middle ear exudates, and bone tissues. The drug is primarily metabolized in the liver, with metabolites exhibiting little or no antimicrobial activity. Under normal conditions, the major route of elimination is the liver, with renal elimination contributing only to a small degree. The degree of modification of josamycin pharmacokinetics by renal insufficiency or hepatic disease is usually not considered clinically relevant.
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| Toxicity/Toxicokinetics |
Toxicological studies of josamycin demonstrate a favorable safety profile at therapeutic doses. As a protein synthesis inhibitor, josamycin is itself toxic to humans and hepatotoxic, which hinders efforts to increase its blood concentrations. Intravenous josamycin is associated with a higher incidence of serious side effects. Oral administration allows for a delicate balance between tissue affinity and metabolism, thereby minimizing side effects while ensuring efficacy. The hepatotoxic properties of josamycin have limited efforts to increase its blood concentrations. This product is for research use only and is not intended for human therapeutic applications. Standard laboratory safety practices and appropriate personal protective equipment should be used when handling.
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| References |
[1]. Kinetics of macrolide action: the Josamycin and erythromycin cases. J Biol Chem. 2004 Dec 17;279(51):53506-15.
[2]. https://pubchem.ncbi.nlm.nih.gov/#query=11033-19-5 |
| Molecular Formula |
C42H69NO15.HCL
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|---|---|
| Molecular Weight |
864.455900000001
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| Exact Mass |
863.443
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| Elemental Analysis |
C, 58.36; H, 8.16; Cl, 4.10; N, 1.62; O, 27.76
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| CAS # |
11033-19-5
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| Related CAS # |
16846-24-5 (free); 11033-19-5 (HCl); 31674-19-8 (propionate)
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| PubChem CID |
74083959
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
59
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| Complexity |
1390
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| Defined Atom Stereocenter Count |
16
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| SMILES |
C[C@@H]1C/C=C/C=C/[C@@H]([C@@H](C[C@@H]([C@@H]([C@H]([C@@H](CC(=O)O1)OC(=O)C)OC)O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)C)O[C@H]3C[C@@]([C@H]([C@@H](O3)C)OC(=O)CC(C)C)(C)O)N(C)C)O)CC=O)C)O.Cl
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| InChi Key |
TYHGHVDZSRXAKD-XLSWTIJLSA-N
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| InChi Code |
InChI=1S/C42H69NO15.ClH/c1-23(2)19-32(47)56-40-27(6)53-34(22-42(40,8)50)57-37-26(5)54-41(36(49)35(37)43(9)10)58-38-29(17-18-44)20-24(3)30(46)16-14-12-13-15-25(4)52-33(48)21-31(39(38)51-11)55-28(7)45;/h12-14,16,18,23-27,29-31,34-41,46,49-50H,15,17,19-22H2,1-11H3;1H/b13-12+,16-14+;/t24-,25-,26-,27+,29+,30+,31-,34+,35-,36-,37-,38+,39+,40+,41+,42-;/m1./s1
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| Chemical Name |
[(2S,3S,4R,6S)-6-[(2R,3S,4R,5R,6S)-6-[[(4R,5S,6S,7R,9R,10R,11E,13E,16R)-4-acetyloxy-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)-1-oxacyclohexadeca-11,13-dien-6-yl]oxy]-4-(dimethylamino)-5-hydroxy-2-methyloxan-3-yl]oxy-4-hydroxy-2,4-dimethyloxan-3-yl] 3-methylbutanoate;hydrochloride
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| Synonyms |
Josamycin HCl; Leucomycin A3 hydrochloride; Josamycin HCl salt; 11033-19-5; RefChem:1087904; Josamycin hydrochloride; Leucomycin A(sub 3) hydrochloride; Josamycin hydrochloride
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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) |
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 | 1.1568 mL | 5.7840 mL | 11.5679 mL | |
| 5 mM | 0.2314 mL | 1.1568 mL | 2.3136 mL | |
| 10 mM | 0.1157 mL | 0.5784 mL | 1.1568 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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