| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Josamycin propionate exerts its antibacterial effect by binding to the 50S subunit of bacterial ribosomes, inhibiting bacterial protein synthesis. As a 16-membered ring macrolide antibiotic, this compound exhibits antibacterial activity against various pathogens including Gram-positive cocci, Haemophilus influenzae, and Mycoplasma pneumoniae. The KEGG database classifies it as a CYP3A/CYP3A4 enzyme inhibitor, suggesting it may affect the metabolism of other drugs by inhibiting hepatic drug-metabolizing enzymes.
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|---|---|
| ln Vitro |
Josamycin propionate exhibits antibacterial activity against various pathogens in vitro. Its antibacterial spectrum covers Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus (including strains resistant to penicillin and erythromycin), Haemophilus influenzae, and Mycoplasma pneumoniae. In vitro pharmacological studies have shown that high concentrations of josamycin propionate (1×10⁻³ g/mL) slightly inhibit contractions of isolated guinea pig ileum induced by acetylcholine or barium chloride, while having no effect on acetylcholine-induced contractions of isolated guinea pig tracheal muscle.
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| ln Vivo |
Josamycin propionate is rapidly absorbed in vivo after oral administration and distributes at high concentrations to various tissues, including the lung, liver, kidney, and spleen. In rat pharmacokinetic studies, antibacterial activity assays showed that following oral administration of josamycin propionate, the time to peak plasma concentration (Tmax) was 2-4 hours, with concentrations then declining slowly, whereas josamycin reached peak levels at 1 hour followed by a rapid decrease. Radioactivity assays demonstrated that plasma and tissue radioactivity concentrations produced by oral josamycin propionate were more than twice those of josamycin. Clinical studies have shown that healthy volunteers receiving 1 g of josamycin propionate achieved a mean peak plasma concentration of approximately 1.02 μg/mL (parent drug) with a Tmax of approximately 1.5 hours.
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| Enzyme Assay |
In vitro enzyme/receptor binding studies for josamycin propionate can be conducted using the following protocol: (1) CYP3A4 inhibition activity assay: Incubate human liver microsomes or recombinant CYP3A4 enzyme with varying concentrations of josamycin propionate (e.g., 0.1-100 μM) at 37°C, initiate the reaction by adding CYP3A4-specific fluorescent substrate (e.g., 7-benzyloxy-4-trifluoromethylcoumarin), and detect metabolite formation using a fluorescence plate reader; (2) Data calculation: Calculate enzyme activity inhibition rates and IC₅₀ values based on changes in fluorescence intensity; (3) Positive control: Use ketoconazole as a strong CYP3A4 inhibitor control.
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| Cell Assay |
(1) Cell culture: Culture target bacterial strains (e.g., Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes) in Müeller-Hinton broth at 37°C with shaking until the logarithmic growth phase; (2) MIC determination: Use the microbroth dilution method with serial 2-fold dilutions of josamycin propionate (0.06-128 μg/mL), mix with bacterial suspension adjusted to 0.5 McFarland turbidity standard, incubate at 37°C for 18-24 hours, and read minimum inhibitory concentration (MIC); (3) Time-kill curve: Inoculate bacteria in media containing varying drug concentrations, sample at 0, 2, 4, 6, 8, and 24 hours for colony counting; (4) Data analysis: Calculate MIC₉₀, MIC₅₀, and minimum bactericidal concentration (MBC).
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| Animal Protocol |
(1) Animal model: Use Sprague-Dawley rats for pharmacokinetic and tissue distribution studies; (2) Dosing regimen: Administer josamycin propionate by oral gavage at doses of 100-1000 mg/kg body weight; (3) Sample collection: Collect blood samples at various time points (0.5, 1, 2, 4, 6, 24 hours) after administration, and euthanize some animals to collect tissues including lung, liver, kidney, and spleen; (4) Sample analysis: Detect drug concentrations in plasma and tissues using microbial agar diffusion assays (antibacterial activity) and liquid scintillation counting (radioactivity) with ¹⁴C-labeled drug; (5) Data analysis: Calculate pharmacokinetic parameters (Cmax, Tmax, t₁/₂, AUC) and characterize tissue distribution.
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| ADME/Pharmacokinetics |
Josamycin propionate is rapidly absorbed after oral administration, reaching peak plasma and tissue concentrations in rats at 2-4 hours, followed by a slow decline. The drug is widely distributed in tissues, with concentrations in the lung, liver, kidney, and spleen being more than twice those of josamycin. In healthy volunteers, the peak plasma concentration of the parent drug josamycin is approximately 1.02 μg/mL, with a Tmax of approximately 1.5 hours. The drug is primarily excreted via bile and urine, with radioactivity recoveries of 21.8% in urine and 60.2% in feces within 4 days after oral administration. Antibacterial activity detected in urine accounts for only 0.65% of the administered dose, indicating that excreted materials are mainly inactive metabolites. The pharmacokinetics of this drug exhibit significant intra- and inter-individual variability, with peak concentrations and AUC values varying up to 10-fold between individuals and approximately 3-fold within individuals.
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| Toxicity/Toxicokinetics |
Toxicological studies of josamycin propionate demonstrate a favorable safety profile at therapeutic doses. In rats and mice, oral doses up to 1000 mg/kg produced no measurable effects on behavior, motor coordination, locomotor activity, or conditioned avoidance responses. Central nervous system safety studies showed that intracerebroventricular injection of josamycin propionate induced abnormal gait, clonus, and jumping in mice, with a 50% convulsant dose of 11.0 mg/kg. Regarding the cardiovascular system, intravenous administration of ≥10 mg/kg produced dose-dependent decreases in heart rate and blood pressure in anesthetized dogs, along with increased carotid and femoral artery blood flow. Intravenous administration at 100 mg/kg caused respiratory depression, decreased heart rate and blood pressure, reduced wave heights in P, Q, and ST waves, and prolonged P-Q, P-R, and P-P intervals on ECG, with these changes resolving after 90 minutes. Common clinical adverse reactions include gastrointestinal symptoms such as loss of appetite, nausea, vomiting, abdominal distension, abdominal pain, and diarrhea, with occasional allergic reactions. The drug is contraindicated in patients with hypersensitivity to this product or other macrolide antibiotics, and concomitant use with ergotamine should be avoided. Storage should be protected from light and sealed, with a tentative expiration period of 2 years.
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| References |
[1]. https://pubchem.ncbi.nlm.nih.gov/compound/10395904
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| Molecular Formula |
C45H73NO16
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|---|---|
| Molecular Weight |
884.06
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| Exact Mass |
883.493
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| Elemental Analysis |
C, 61.14; H, 8.32; N, 1.58; O, 28.96
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| CAS # |
31674-19-8
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| PubChem CID |
10395904
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| Appearance |
Typically exists as solids at room temperature
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| Density |
1.19g/cm3
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| Boiling Point |
946.1ºC at 760 mmHg
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| Flash Point |
526ºC
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| LogP |
3.974
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
62
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| Complexity |
1520
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| Defined Atom Stereocenter Count |
16
|
| SMILES |
CC(CC(OC1C(C)OC(OC2C(C)OC(OC3C(CC=O)CC(C)C(O)C=CC=CCC(C)OC(=O)CC(OC(=O)C)C3OC)C(OC(CC)=O)C2N(C)C)CC1(C)O)=O)C |t:27,29|
|
| InChi Key |
NBWASFCRCRXRKF-VGOAISAMSA-N
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| InChi Code |
InChI=1S/C45H73NO16/c1-13-34(50)59-42-38(46(10)11)39(61-37-24-45(9,53)43(29(7)56-37)60-35(51)21-25(2)3)28(6)57-44(42)62-40-31(19-20-47)22-26(4)32(49)18-16-14-15-17-27(5)55-36(52)23-33(41(40)54-12)58-30(8)48/h14-16,18,20,25-29,31-33,37-44,49,53H,13,17,19,21-24H2,1-12H3/b15-14+,18-16+/t26-,27-,28-,29+,31+,32+,33-,37+,38+,39-,40+,41+,42-,43+,44+,45-/m1/s1
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| Chemical Name |
[(2S,3S,4R,6S)-6-[(2R,3S,4S,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)-2-methyl-5-propanoyloxyoxan-3-yl]oxy-4-hydroxy-2,4-dimethyloxan-3-yl] 3-methylbutanoate
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| Synonyms |
31674-19-8; 911QFM8O20; JOSAMYCIN 2A-PROPANOATE; RefChem:1087903; josamycin propionate;
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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 | 1.1311 mL | 5.6557 mL | 11.3114 mL | |
| 5 mM | 0.2262 mL | 1.1311 mL | 2.2623 mL | |
| 10 mM | 0.1131 mL | 0.5656 mL | 1.1311 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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