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Purity: ≥98%
Gamithromycin (also known as ML-1709460) is an antimicrobial agent that is used in animals. It can inhibit the growth of MmmSC strains B237 and Tan8 with MICs of 0.00012 and 0.00006 μg/mL, respectively. Gamithromycin is active in vitro against the bacterial agents most commonly associated with bronchopneumonia in older foals. Mycoplasma mycoides mycoides Small Colony (MmmSC) is the causative agent of contagious bovine pleuropneumonia (CBPP), which is responsible for major economic losses in sub-Saharan Africa. Current control relies on live attenuated vaccines, which are of limited efficacy, and antimicrobials are now being assessed as an alternative or adjunct to vaccination.
| Targets |
MmmSC strain B237(MIC= 0.00012 μg/mL);MmmSC strain Tan8(MIC= 0.00006μg/mL )
Bacterial 50S ribosomal subunit (inhibits bacterial protein synthesis) [1] |
|---|---|
| ln Vitro |
- Against Mycoplasma mycoides subsp. mycoides Small Colony (MmmSC) strains (n=10), gamithromycin showed antibacterial activity with MIC values ranging from 0.0625 to 0.25 μg/mL. The MIC50 and MIC90 were 0.125 μg/mL and 0.25 μg/mL, respectively, determined by broth microdilution assay [1]
- Time-kill curves demonstrated that gamithromycin (at 2× MIC) exhibited bacteriostatic activity against MmmSC, with no significant bactericidal effect (≤1 log10 CFU/mL reduction) after 48 hours of incubation [1] When comparing serum to artificial medium, the minimum inhibitory concentration (MIC) values for gamithromycin, tylosin, and tilmicosin against MmmSC strain B237 are 64-, 8-, and 64-fold lower, respectively, at an initial inoculum size of 106 cfu/mL. For Tan8, a similar pattern shows up. Gamithromycin's minimum inhibitory concentration (MIC) is higher in heat-inactivated serum compared to untreated serum or synthetic medium[1]. |
| ln Vivo |
- In foals with mild to moderate bronchopneumonia (n=48), a single subcutaneous injection of gamithromycin (6 mg/kg) resulted in clinical improvement. At day 7 post-treatment, 83% of foals showed resolution of fever, 79% had reduced cough severity, and 75% had normalized respiratory rates, compared to 50% in the placebo group [2]
- Bacterial culture from tracheobronchial aspirates (TBA) showed that 67% of gamithromycin-treated foals had negative results for pathogenic bacteria (e.g., Streptococcus equi subsp. zooepidemicus) at day 7, versus 33% in the placebo group [2] In comparison to control foals (32 of 41; 78%), the percentage of foals that recover without requiring a change in treatment is significantly (P<0.048) higher for foals treated with gamithromycin (GAM) (38 of 40; 95%) or AZM-RIF (39 of 40; 98%). When compared to control foals, foals treated with Gamithromycin (GAM) or AZM-RIF had significantly lower clinical scores, fewer abscesses, and abscess scores after one and two weeks of treatment. On the third week of treatment, the WBC count of foals treated with Gamithromycin (GAM) is significantly higher than that of foals treated with AZM-RIF[2]. |
| Cell Assay |
- MIC determination for MmmSC: Bacteria were cultured in modified Hayflick’s medium and adjusted to 1×10^6 CFU/mL. Serial dilutions of gamithromycin (0.0078–1 μg/mL) were prepared in 96-well plates, inoculated with bacteria, and incubated at 37°C with 5% CO2 for 7 days. MIC was defined as the lowest concentration with no visible growth [1]
- Time-kill assay: MmmSC cultures (5×10^5 CFU/mL) were exposed to gamithromycin (0.25–1 μg/mL, 1× and 2× MIC) and incubated at 37°C. Aliquots were plated at 0, 24, and 48 hours to enumerate viable colonies (CFU/mL) [1] A macrodilution technique is used to determine the minimum inhibitory concentrations (MICs) of gamithromycin, tylosin, and tilmicosin against MmmSC strains B237 and Tan8. Each antimicrobial dilution receives equal volumes of logarithmic phase MmmSC culture to provide an inoculum size of 107 cfu/mL, or the intended initial titre for subsequent time-kill assays, in a volume of 4 mL. At 37°C, cultures are incubated for 24 hours. Samples are taken out at 0 and 24 hour intervals, and they are serially diluted 10-fold to 10-5. Aliquots (10 μL) of every dilution are moved to solid medium, and colonies are counted from the dilution that yields between 30 and 300 colonies per plate after at least 4 days of incubation at 37°C in a humidified atmosphere with 5% carbon dioxide in the air. The lowest antimicrobial concentration (MIC) that stops a 24-hour increase in cfu/mL is defined as counts converted to cfu/mL[1]. |
| Animal Protocol |
Foals exhibiting pulmonary abscesses on ultrasonographic examinations are randomized into three treatment groups: (1) semimembranosus/semitendinosus muscles are treated with gamithromycin at a dose of 6.0 mg/kg body weight once a week (GAM; n = 40); (2) azithromycin at a dose of 10 mg/kg PO once daily combined with rifampin at a dose of 10 mg/kg PO once daily (AZM-RIF; n = 40); and (3) no antimicrobial treatment (controls; n = 41). To ensure that every foal in every treatment group receives the same daily manipulation, each foal receives acetylcysteine at a dose of 10 mg/kg PO per day[2].
- Bronchopneumonia foal model: Foals (1–6 months old) with clinical signs (fever ≥38.5°C, cough, abnormal lung auscultation) and positive TBA bacterial culture were included. Gamithromycin (6 mg/kg) was administered as a single subcutaneous injection. Clinical parameters (temperature, respiratory rate, cough score) and TBA bacterial counts were evaluated at days 0, 1, 3, 7, and 14 [2] |
| ADME/Pharmacokinetics |
In foals, the peak plasma concentration (Cmax) 2 hours after a single subcutaneous injection of Gamithromycin (6 mg/kg) was 1.2 μg/mL. The drug has high lung permeability, with a lung/plasma concentration ratio of 8:1 at 24 hours. The plasma half-life (t1/2) is approximately 36 hours.[2]
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| References | |
| Additional Infomation |
Gamithromycin is a macrolide antibiotic with the molecular formula C40H76N2O12. It is used to treat respiratory diseases in beef cattle and non-lactating dairy cattle caused by Mannella hemolyticus, Pasteurella multocida, Histoplasma haemolyticus, and Mycoplasma bovis. This compound is also approved in Europe for the treatment of hoof rot in sheep caused by Fusobacterium nodosa and Fusobacterium nodosa. It has antibacterial and protein synthesis inhibitory effects. It is a macrolide antibiotic and also a monosaccharide derivative. Gamithromycin is an antibiotic used in cattle. Indications: Cattle: Treatment and prevention of bovine respiratory disease (BRD) caused by Mannella hemolyticus, Pasteurella multocida, and Histoplasma haemolyticus. The presence of the disease in the herd should be determined before prophylactic administration. Pigs: Used to treat swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Bordetella bronchiseptica. Sheep: Used to treat infectious plantar dermatitis (hoof rot) caused by highly virulent Clostridium nodosa and Clostridium necrophorum, requiring systemic treatment.
- Gamithromycin is a semi-synthetic macrolide antibiotic developed for veterinary use, primarily targeting Gram-positive bacteria and some Gram-negative respiratory pathogens [1][2] - Its mechanism of action is to bind to the bacterial 50S ribosomal subunit, inhibiting peptide chain elongation and bacterial protein synthesis [1] |
| Molecular Formula |
C40H76N2O12
|
|---|---|
| Molecular Weight |
777.05
|
| Exact Mass |
776.539
|
| Elemental Analysis |
C, 61.83; H, 9.86; N, 3.61; O, 24.71
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| CAS # |
145435-72-9
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| Related CAS # |
145435-72-9;
|
| PubChem CID |
59364992
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| Appearance |
Solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
833.0±65.0 °C at 760 mmHg
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| Flash Point |
457.6±34.3 °C
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| Vapour Pressure |
0.0±0.6 mmHg at 25°C
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| Index of Refraction |
1.535
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| LogP |
3.89
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
54
|
| Complexity |
1180
|
| Defined Atom Stereocenter Count |
18
|
| SMILES |
O([C@@]1([H])[C@@]([H])([C@]([H])(C([H])([H])[C@@]([H])(C([H])([H])[H])O1)N(C([H])([H])[H])C([H])([H])[H])O[H])[C@@]1([H])[C@@](C([H])([H])[H])(C([H])([H])[C@@]([H])(C([H])([H])[H])N(C([H])([H])C([H])([H])C([H])([H])[H])C([H])([H])[C@]([H])(C([H])([H])[H])[C@]([H])([C@@](C([H])([H])[H])([C@@]([H])(C([H])([H])C([H])([H])[H])OC([C@]([H])(C([H])([H])[H])[C@]([H])([C@]1([H])C([H])([H])[H])O[C@@]1([H])C([H])([H])[C@](C([H])([H])[H])([C@]([H])([C@]([H])(C([H])([H])[H])O1)O[H])OC([H])([H])[H])=O)O[H])O[H])O[H]
|
| InChi Key |
VWAMTBXLZPEDQO-UZSBJOJWSA-N
|
| InChi Code |
InChI=1S/C40H76N2O12/c1-15-17-42-21-22(3)33(44)40(11,48)29(16-2)52-36(46)26(7)32(53-30-20-39(10,49-14)34(45)27(8)51-30)25(6)35(38(9,47)19-23(42)4)54-37-31(43)28(41(12)13)18-24(5)50-37/h22-35,37,43-45,47-48H,15-21H2,1-14H3/t22-,23+,24+,25-,26+,27-,28-,29+,30-,31+,32-,33+,34-,35+,37-,38+,39+,40+/m0/s1
|
| Chemical Name |
(2R,3S,4R,5S,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4,10-trihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,8,10,12,14-hexamethyl-7-propyl-1-oxa-7-azacyclopentadecan-15-one
|
| Synonyms |
Gamithromycin; GAM, ML-1709460; Gamithromycin; 145435-72-9; gamitromicina; gamithromycinum; ML-1709,460; ML-460; ML-1,709,460; (2R,3S,4R,5S,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4,10-trihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,8,10,12,14-hexamethyl-7-propyl-1-oxa-7-azacyclopentadecan-15-one; ML 1709460; ML1709460;
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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) |
DMSO : ~100 mg/mL ( ~128.69 mM )
Ethanol : ~100 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (3.22 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (3.22 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2869 mL | 6.4346 mL | 12.8692 mL | |
| 5 mM | 0.2574 mL | 1.2869 mL | 2.5738 mL | |
| 10 mM | 0.1287 mL | 0.6435 mL | 1.2869 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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