Erythromycin Ethylsuccinate is a potent and broad-spectrum antibiotic belonging to a group of drugs called macrolide antibiotics, it is produced by actinomycete Streptomyces erythreus and is an inhibitor of protein translation and mammalian mRNA splicing. It acts by binding to bacterial 50S ribosomal subunits and inhibits RNA-dependent protein synthesis by blockage of transpeptidation and/or translocation reactions, without affecting synthesis of nucleic acid, thus inhibiting growth of gram negative and gram positiove bacteria. Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections.
Physicochemical Properties
| Molecular Formula | C43H75NO16 |
| Molecular Weight | 862.0527 |
| Exact Mass | 861.508 |
| Elemental Analysis | C, 59.91; H, 8.77; N, 1.62; O, 29.69 |
| CAS # | 1264-62-6 |
| Related CAS # | Erythromycin;114-07-8;Erythromycin ethylsuccinate-13C,d3 |
| PubChem CID | 443953 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 874.1±65.0 °C at 760 mmHg |
| Melting Point | 219-224ºC |
| Flash Point | 482.4±34.3 °C |
| Vapour Pressure | 0.0±0.6 mmHg at 25°C |
| Index of Refraction | 1.529 |
| Source | Saccharopolyspora erythraea |
| LogP | 4.1 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 17 |
| Rotatable Bond Count | 14 |
| Heavy Atom Count | 60 |
| Complexity | 1450 |
| 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])OC(C([H])([H])C([H])([H])C(=O)OC([H])([H])C([H])([H])[H])=O)[C@@]1([H])[C@@](C([H])([H])[H])(C([H])([H])[C@@]([H])(C([H])([H])[H])C([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)O[H] |
| InChi Key | NSYZCCDSJNWWJL-YXOIYICCSA-N |
| InChi Code | InChI=1S/C43H75NO16/c1-15-29-43(11,52)36(48)24(5)33(47)22(3)20-41(9,51)38(25(6)34(26(7)39(50)57-29)59-32-21-42(10,53-14)37(49)27(8)56-32)60-40-35(28(44(12)13)19-23(4)55-40)58-31(46)18-17-30(45)54-16-2/h22-29,32,34-38,40,48-49,51-52H,15-21H2,1-14H3/t22-,23-,24+,25+,26-,27+,28+,29-,32+,34+,35-,36-,37+,38-,40+,41-,42-,43-/m1/s1 |
| Chemical Name | (2S,3R,4S,6R)-4-(dimethylamino)-2-(((3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-7,12,13-trihydroxy-4-(((2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl)oxy)-3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecan-6-yl)oxy)-6-methyltetrahydro-2H-pyran-3-yl ethyl succinate |
| Synonyms | Erythromycin ethylsuccinate; E-Mycin E; E.E.S; Wyamycin; Wyamycin E; |
| 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 | Macrolide antibiotic; Antiviral; HIV-1 |
| ln Vitro | Macrophages (MPhis) are a major source of HIV-1 especially in patients with tuberculosis. There are MPhis that are permissive and those that restrict HIV-1. Regulation of hematopoietic cell kinase (Hck) activity and selective expression of CCAAT enhancer binding protein beta (C/EBPbeta) isoforms greatly contribute to determine distinct susceptibility of MPhis to HIV-1. Resistance is attributable to reduced expression of Hck and augmented expression of an inhibitory small isoform of C/EBPbeta. Derivatives of erythromycin A (EMA) EM201 and EM703 inhibit the replication of HIV-1 in tissue MPhis, at posttranscriptional and translational levels. We demonstrate that EM201 and EM703 convert tissue MPhis from HIV-1 susceptible to HIV-1 resistant through down-regulation of Hck and induction of small isoforms of C/EBPbeta. These drugs inhibit p38MAPK activation which is expressed only in susceptible tissue MPhis. Activated CD4(+)T cells stimulate the viral replication in HIV-1 resistant MPhis through down-regulation of small isoforms of C/EBPbeta via activation of ERK1/2. EM201 and EM703 can inhibit the MAPK activation and inhibit the burst of viral replication produced when CD4(+)T cells and MPhis interact. These EM derivatives may be highly beneficial for repression of residual HIV-1 in the lymphoreticular system of HIV-1-infected patients and offer great promise for the creation of new anti-HIV drugs for the future treatment of AIDS patients [4]. |
| ln Vivo | In Sweden there are several reports of mares developing acute colitis while their foals were being treated orally for Rhodococcus equi pneumonia with the combination of erythromycin and rifampicin. In this study 6 adult horses were given low oral dosages of these antibiotics, singly or in combination. Within 3 days post administration of erythromycin, in one case in combination with rifampicin, 2 horses developed severe colitis (one fatal). Clostridium difficile was isolated from one of the horses, whereas no specific pathogens were isolated from the other. Both horses had typical changes in blood parameters seen in acute colitis. Clostridium difficile was also isolated from the faeces of a third horse given an even lower dosage of erythromycin in combination with rifampicin. This horse developed very mild clinical symptoms and recovered spontaneously. In the fourth horse given erythromycin only, very high numbers of Clostridium perfringens were isolated. The horses given rifampicin only did not develop any clinical symptoms and there were no major changes in their faecal flora. In conclusion, it has been demonstrated that low dosages of erythromycin ethylsuccinate can induce severe colitis in horses associated with major changes of the intestinal microflora. Clostridium difficile has been demonstrated as a potential aetiological agent in antibiotic-induced acute colitis [5]. |
| Enzyme Assay | HIV-1 Strain and Infection. M-tropic HIV-1 strain, HIV-1BaL, was collected from culture supernatant of the HIV-1 strain-infected M-MΦs as a viral resource. Mo-derived MΦs were incubated for 2 h at 37°C with 100 pg/ml p24 antigen of DNase-treated viral supernatant (p24, the 50% tissue culture infective dose (TCID50) and multiplicity of infection (MOI) are 50 ng/ml, ∼3,000 and 0.05, respectively) and then cultured in RPMI MEDIUM 1640 containing 10% FCS and CSF. If necessary, the viral inoculum was pretreated with 100 μM AZT for 2 h at 4°C. Fresh culture medium containing CSF was added every 3–4 d (20% of the volume). Heat-inactivated virus (1 h, 56°C) was used as negative control. Viral production was assayed by sequential measurement of p24 antigen in supernatants by an ELISA using a combination of two antibodies; anti-gag-p24 monoclonal antibody (Nu24) and peroxidase-labeled 10B5, or the RETRO-TEK HIV-1 p24 antigen ELISA kit for high-affinity detection of low levels of p24 antigen[4]. |
| Cell Assay | Coculture of HIV-1 Infected GM-MΦs with the Activated CD4+T Cells. CD4+ T cells were positively isolated from CD14− PBMCs using a MACS with anti-CD4 mAb coated microbeads. The selected population was >93% positive for CD3 and CD4. Activated CD4+ T cells were prepared by stimulation with PHA and cultured with IL-2 (30 unit/ml). GM-MΦs were incubated for 2 h at 37°C with 100 pg/ml p24 antigen of DNase-treated viral supernatant, washed twice, and then cocultured with the activated CD4+ T cells in the presence of IL-2 [4]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion ERYTHROMYCIN ETHYLSUCCINATE IS PARTIALLY DISSOCIATED IN INTESTINE; BOTH ERYTHROMYCIN & UNDISSOCIATED ESTER ARE ABSORBED &, IN THE BLOOD, THE ESTER IS HYDROLYZED TO RELEASE FREE ERYTHROMYCIN. ERYTHROMYCIN ETHYLSUCCINATE...IS ADEQUATELY ABSORBED FOLLOWING ORAL ADMINISTRATION, PARTICULARLY WHEN THE STOMACH IS EMPTY. PEAK CONCENTRATIONS IN PLASMA ARE 1.5 UG/ML (0.5 UG/ML OF BASE) 1 TO 2 HR AFTER ADMINISTRATION OF A 500 MG TABLET. IN PATIENTS, MEAN BILE LEVELS OF ERYTHROMYCIN WERE APPROXIMATELY 10 TIMES HIGHER THAN CORRESPONDING SERUM CONCN 1 HR AFTER IV (ERYTHROMYCIN LACTOBIONATE) & IM (ERYTHROMYCIN SUCCINATE) INJECTION. IN HEALTHY ADULT SUBJECTS & IN ADULT PATIENTS WITH BRONCHIAL INFECTIONS, PHARMACOKINETICS OF VARIOUS FORMULATIONS OF ERYTHROMYCIN WERE STUDIED. ERYTHROMYCIN ETHYLSUCCINATE WAS BETTER THAN ERYTHROMYCIN STEARATE FOR ORAL TREATMENT IN THAT IT WAS RAPIDLY & CONSISTENTLY ABSORBED. |
| References |
[1]. Erythromycin. Med Clin North Am. 1982 Jan;66(1):79-89. [2]. Activity of azithromycin or erythromycin in combination with antimalarial drugs against multidrug-resistant Plasmodium falciparum in vitro. Acta Trop. 2006 Dec;100(3):185-91. Epub 2006 Nov 28. [3]. Construction of universal quantitative models for determination of roxithromycin and erythromycin ethylsuccinate in tablets from different manufacturers using near infrared reflectance spectroscopy. J Pharm Biomed Anal. 2006 May 3;41(2):373-84. [4]. Erythromycin derivatives inhibit HIV-1 replication in macrophages through modulation of MAPK activity to induce small isoforms of C/EBPbeta. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12509-14.[5]. The association of erythromycin ethylsuccinate with acute colitis in horses in Sweden. Equine Vet J. 1997 Jul;29(4):314-8. |
| Additional Infomation |
Erythromycin ethylsuccinate is a erythromycin derivative that is erythromycin A in which the hydroxy group at position 3R is substituted by a (4-ethoxy-4-oxobutanoyl)oxy group. It is used for the treatment of a wide variety of bacterial infections. It is a succinate ester, a cyclic ketone, an erythromycin derivative and an ethyl ester. It is functionally related to an erythromycin A. Erythromycin Ethylsuccinate is the ethylsuccinate salt form of erythromycin, a broad-spectrum, topical macrolide antibiotic with antibacterial activity. Erythromycin ethylsuccinate diffuses through the bacterial cell membrane and reversibly binds to the 50S subunit of the bacterial ribosome. This prevents bacterial protein synthesis. Erythromycin ethylsuccinate may be bacteriostatic or bactericidal in action, depending on the concentration of the drug at the site of infection and the susceptibility of the organism involved. A macrolide antibiotic, produced by Streptomyces erythreus. This compound is an ester of erythromycin base and succinic acid. It acts primarily as a bacteriostatic agent. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. See also: Erythromycin (has active moiety); Erythromycin ethylsuccinate; sulfisoxazole acetyl (component of). Therapeutic Uses Antibiotics, Macrolide; Enzyme Inhibitors; Gastrointestinal Agents; Protein Synthesis Inhibitors RELATIVELY NONIRRITATING...& THUS IS WELL SUITED TO IM INJECTION. ...ITS ACTIONS & USES ARE ESSENTIALLY THOSE OF ERYTHROMYCIN...INTO WHICH IT IS CONVERTED IN THE BODY. ERYTHROMYCIN IS...ANTIMICROBIAL... ERYTHROMYCIN IS.../ACTIVE/ AGAINST MOST GRAM-POSITIVE BACTERIA, MANY ANAEROBES...& LEGIONNAIRE'S BACILLUS. /ERYTHROMYCIN/ ERYTHROMYCIN MAY BE...BACTERIOSTATIC OR BACTERICIDAL DEPENDING ON NATURE OF MICROORGANISM & CONCN OF DRUG. ...MOST EFFECTIVE IN VITRO AGAINST GRAM-POSITIVE COCCI SUCH AS STAPHYLOCOCCUS AUREUS (PENICILLIN G SENSITIVE OR RESISTANT), GROUP A STREPTOCOCCI, ENTEROCOCCI & PNEUMOCOCCI; MANY GRAM-POSITIVE BACILLI... /ERYTHROMYCIN/ A REVIEW OF THE ANTIMICROBIAL SPECTRUM, PHARMACOLOGY & THERAPEUTIC USE OF ERYTHROMYCIN & ITS DERIVATIVES. (REF 24). |
Solubility Data
| Solubility (In Vitro) |
DMSO : ≥ 50 mg/mL (~58.00 mM) Ethanol :≥ 33.33 mg/mL (~38.66 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.90 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 (2.90 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1600 mL | 5.8001 mL | 11.6003 mL | |
| 5 mM | 0.2320 mL | 1.1600 mL | 2.3201 mL | |
| 10 mM | 0.1160 mL | 0.5800 mL | 1.1600 mL |