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.
Physicochemical Properties
| 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 |
| CAS # | 145435-72-9 |
| Related CAS # | 145435-72-9; |
| PubChem CID | 59364992 |
| Appearance | Solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 833.0±65.0 °C at 760 mmHg |
| Flash Point | 457.6±34.3 °C |
| Vapour Pressure | 0.0±0.6 mmHg at 25°C |
| Index of Refraction | 1.535 |
| LogP | 3.89 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 14 |
| Rotatable Bond Count | 9 |
| 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; ML 1709460; ML1709460; |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | MmmSC strain B237(MIC= 0.00012 μg/mL);MmmSC strain Tan8(MIC= 0.00006μg/mL ) |
| ln Vitro | 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 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 | 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]. |
| References |
[1]. In vitro pharmacodynamics of gamithromycin against Mycoplasma mycoides subspecies mycoides Small Colony. Vet J. 2013 Sep;197(3):806-11. [2]. Efficacy of Gamithromycin for the Treatment of Foals with Mild to Moderate Bronchopneumonia. J Vet Intern Med. 2015 Jan-Feb; 29(1): 333–338. |
| Additional Infomation |
Gamithromycin is a macrolide antibiotic with formula C40H76N2O12. It is used for the treatment of of bovine respiratory disease caused by Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma bovis in beef and non-lactating dairy cattle. The compound is also licensed in Europe for the treatment of footrot in sheep caused by Dichelobacter nodosus and Fusobacterium nodosus. It has a role as an antibacterial drug and a protein synthesis inhibitor. It is a macrolide antibiotic and a monosaccharide derivative. Gamithromycin is an antibiotic used in cattle. Drug Indication CattleTreatment and metaphylaxis of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida and Histophilus somni. The presence of the disease in the herd should be established before metaphylactic use. PigsTreatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis and Bordetella bronchiseptica. SheepTreatment of infectious pododermatitis (foot rot) associated with virulent Dichelobacter nodosus and Fusobacterium necrophorum requiring systemic treatment. |
Solubility Data
| 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. 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. 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 corn oil and mix evenly.. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (3.22 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |