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Description: Sigapedil (Erythromycin gluceptate) is a macrolide antibiotic isolated from actinomycete Streptomyces erythreus, acting by binding to bacterial 50S ribosomal subunits and inhibiting RNA-dependent protein synthesis by blockage of transpeptidation and/or translocation reactions, without affecting synthesis of nucleic acid. It exhibits a broad spectrum of antimicrobial activity as well as antitumor and neuroprotective effects.
Physicochemical Properties
| Molecular Formula | C37H67NO13.C7H14O8 |
| Molecular Weight | 960.108040000001 |
| Exact Mass | 959.53 |
| Elemental Analysis | C, 55.04; H, 8.50; N, 1.46; O, 34.99 |
| CAS # | 23067-13-2 |
| Related CAS # | Erythromycin (aspartate);30010-41-4 |
| PubChem CID | 16051953 |
| Appearance | Solid powder |
| Boiling Point | 818.4ºC at 760 mmHg |
| Flash Point | 448.8ºC |
| Vapour Pressure | 4.94E-31mmHg at 25°C |
| Hydrogen Bond Donor Count | 12 |
| Hydrogen Bond Acceptor Count | 22 |
| Rotatable Bond Count | 13 |
| Heavy Atom Count | 66 |
| Complexity | 1380 |
| Defined Atom Stereocenter Count | 23 |
| SMILES | OC[C@H]([C@H]([C@@H]([C@H]([C@H](C(=O)O)O)O)O)O)O.CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(OC)C2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)[C@](C)(O)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O |
| InChi Key | ZXBDZLHAHGPXIG-VTXLJDRKSA-N |
| InChi Code | InChI=1S/C37H67NO13.C7H14O8/c1-14-25-37(10,45)30(41)20(4)27(39)18(2)16-35(8,44)32(51-34-28(40)24(38(11)12)15-19(3)47-34)21(5)29(22(6)33(43)49-25)50-26-17-36(9,46-13)31(42)23(7)48-26;8-1-2(9)3(10)4(11)5(12)6(13)7(14)15/h18-26,28-32,34,40-42,44-45H,14-17H2,1-13H3;2-6,8-13H,1H2,(H,14,15)/t18-,19-,20+,21+,22-,23+,24+,25-,26+,28-,29+,30-,31+,32-,34+,35-,36-,37-;2-,3-,4+,5-,6-/m11/s1 |
| Chemical Name | (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-(((2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-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-hexamethyloxacyclotetradecane-2,10-dione (2R,3R,4S,5R,6R)-2,3,4,5,6,7-hexahydroxyheptanoate |
| Synonyms | Ilotycin gluceptate; Erythromycin glucoheptonate; Ilotycin glucoheptonate |
| 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 |
| ln Vitro | P. falciparum cannot develop in the presence of erythromycin gluceptate, which has IC50 and IC90 values of 58.2 μM and 104.0 μM, respectively[1]. Erythromycin gluceptate (10 μM, 100 μM; 24 h, 72 h) exhibits anti-inflammatory and antioxidant properties. It also inhibits the accumulation of 4-HNE (p<0.01) and 8-OHdG (p<0.01) and considerably lowers the production of TNF-α (p<0.01) and Iba-1 (p<0.01)[4]. |
| ln Vivo | Erythromycin gluceptate (0.1–50 mg/kg; 30-120 days) reduces tumor growth and increases the amount of time that mice survive after receiving a dose of 5 mg/kg[3]. Even 120 days after inoculation, animals protected by erythromycin gluceptate (gastric intubation; 5 mg/kg) survive; however, a 50 mg/kg dose shortens the mean survival period in tumor-bearing mice by 4-5 days[3]. In the rat model of cerebral ischemia reperfusion injury, erythromycin gluceptate (ih; single injection; 50 mg/kg) exhibits a protective effect[4]. |
| Cell Assay |
Cell Viability Assay[4] Cell Types: Embryos primary cortical neuron (from the cerebral cortices of 17-day-old Sprague-Dawley rat) Tested Concentrations: 10, 100 μM Incubation Duration: 24, 72 hrs (hours) Experimental Results: Improved the viability of cultured neuronal cells in vitro after 3 hrs (hours) oxygen-glucose deprivation (OGD). |
| Animal Protocol |
Animal/Disease Models: Female ddY mice (6weeks old) with EAC cells or CDF mice (6weeks old) with P388 cells[3] Doses: 0.1 mg/kg; 0.5 mg/kg; 10 mg/kg; 30 mg/kg; 50 mg/kg Route of Administration: Gastric intubation; 30-120 days Experimental Results: diminished tumor growth and prolonged the mean survival time of mice from the dose of 5 mg/kg, however, the 50 mg/kg dosage shortened the MST in tumorbearing mice. Animal/Disease Models: Male SD (Sprague-Dawley) rats (8weeks old, 250-300 g)[4] Doses: 50 mg /kg Route of Administration: subcutaneous (sc) single injection Experimental Results: decreased infarct volume and edema volume, improved neurological deficit. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Because of the low levels of erythromycin in breastmilk and safe administration directly to infants, it is acceptable in nursing mothers. The small amounts in milk are unlikely to cause adverse effects in the infant. Monitor the infant for irritability and possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash). One case report and unconfirmed epidemiologic evidence indicates that hypertrophic pyloric stenosis in infants might occur with maternal use of erythromycin during the first two weeks of breastfeeding; however, if it occurs, the frequency is very low and others have questioned this relationship. Infant side effects are unlikely with topical application for acne, although topical application to the nipple may increase the risk of diarrhea in the infant. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.[1] ◉ Effects in Breastfed Infants Pyloric stenosis, vomiting, sedation, poor sucking and poor weight gain probably related to erythromycin in breastmilk was reported in a 3-week-old infant.[4] A cohort study of infants diagnosed with infantile hypertrophic pyloric stenosis found that affected infants were 2.3 to 3 times more likely to have a mother taking a macrolide antibiotic during the 90 days after delivery. Stratification of the infants found the odds ratio to be 10 for female infants and 2 for male infants. All of the mothers of affected infants nursed their infants. Seventy-two percent of the macrolide prescriptions were for erythromycin. However, the authors did not state which macrolide was taken by the mothers of the affected infants.[5] A study comparing the breastfed infants of mothers taking amoxicillin to those taking a macrolide antibiotic found no instances of pyloric stenosis. However, most of the infants exposed to a macrolide in breastmilk were exposed to roxithromycin. Only 2 of the 55 infants exposed to a macrolide were exposed to erythromycin. Adverse reactions occurred in 12.7% of the infants exposed to macrolides which was similar to the rate in amoxicillin-exposed infants. Reactions included rash, diarrhea, loss of appetite, and somnolence.[6] A retrospective database study in Denmark of 15 years of data found a 3.5-fold increased risk of infantile hypertrophic pyloric stenosis in the infants of mothers who took a macrolide during the first 13 days postpartum, but not with later exposure. The proportion of infants who were breastfed was not known, but probably high. The proportion of women who took each macrolide was also not reported.[7] In one telephone follow-up study, mothers reported diarrhea 2 infants and irritability in 2 infants out of 17 infants whose mothers were taking erythromycin during breastfeeding. None of the reactions required medical attention.[8] Two meta-analyses failed to demonstrate a relationship between maternal macrolide use during breastfeeding and infantile hypertrophic pyloric stenosis.[9][10] ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| 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. [3]. Antitumor effect of erythromycin in mice. Chemotherapy. 1995 Jan-Feb. 41(1):59-69. [4]. Neuroprotective effects of erythromycin on cerebral ischemia reperfusion-injury and cell viability after oxygen-glucose deprivation in cultured neuronal cells. Brain Res. 2014 Nov 7. 1588:159-67. |
| Additional Infomation | See also: Erythromycin (has active moiety). |
Solubility Data
| Solubility (In Vitro) | DMSO: > 10 mM |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0415 mL | 5.2077 mL | 10.4155 mL | |
| 5 mM | 0.2083 mL | 1.0415 mL | 2.0831 mL | |
| 10 mM | 0.1042 mL | 0.5208 mL | 1.0415 mL |