| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 1g | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Macrolide antibiotic
EM-523 targets the motilin receptor, a G-protein coupled receptor expressed in the gastrointestinal tract. It acts as a potent motilin receptor agonist. By binding to the motilin receptor, EM-523 mimics the peptide hormone motilin, which leads to duodenal contractions and stimulates gastrointestinal motility. The compound has no antibacterial activity, distinguishing it from erythromycin A and its other derivatives. |
|---|---|
| ln Vitro |
A major drawback of the antibiotic erythromycin A is its extreme acid sensitivity, leading to rapid inactivation in the stomach. The accepted model for degradation in aqueous acidic solution has erythromycin A in equilibrium with erythromycin A enol ether and degrading to anhydroerythromycin A. We report a detailed kinetic study of the acidic degradation of erythromycin A and of erythromycin A 2'-ethyl succinate (the market-leading pediatric prodrug), investigating the reaction rates and degradation products via NMR. This reveals that the accepted mechanism is incorrect and that both the enol ether and the anhydride are in equilibrium with the parent erythromycin. By implication, both the anhydride and enol ether are antibacterially inactive reservoirs for the parent erythromycin. The actual degradation pathway is the slow loss of cladinose from erythromycin A (or erythromycin A 2'-ethyl succinate), which is reported here for the first time in a kinetic study. The kinetic analysis is based on global, nonlinear, simultaneous least-squares fitting of time course concentrations for all species across multiple datasets to integrated rate expressions, to provide robust estimates of the rate constants [2].
In vitro, EM-523 binds to the human motilin receptor with an IC50 of 3.40 nM and shows additional affinity with an IC50 of 224 nM in other assay formats. It acts as a potent motilin receptor agonist, stimulating gastrointestinal smooth muscle contraction. Unlike erythromycin A, it has no antibacterial effect, making it a valuable tool for studying motilin receptor function without the confounding effects of antibiotic activity. |
| ln Vivo |
In vivo, EM-523 stimulates gastrointestinal motor activity via its effect on motilin receptors. As a motilin receptor agonist, it induces duodenal contractions and promotes gastrointestinal motility. The compound has been studied for its potential to treat gastrointestinal motility disorders. Its lack of antibacterial activity reduces the risk of altering the gut microbiome, which is a limitation of erythromycin when used as a prokinetic agent.
|
| Enzyme Assay |
In vitro receptor binding assays for EM-523 use membrane preparations from cells expressing the human motilin receptor. Radiolabeled motilin or a motilin receptor ligand is used as a tracer. Various concentrations of EM-523 are incubated with membranes and radioligand. Bound radioactivity is measured by scintillation counting. IC50 or Ki values are calculated from displacement curves. Functional assays measure motilin receptor-mediated calcium mobilization or GTPγS binding.
|
| Cell Assay |
Cellular assays for EM-523 use cells expressing the motilin receptor. Cells are loaded with a calcium-sensitive fluorescent dye and treated with various concentrations of EM-523. Receptor activation leads to calcium mobilization, which is measured fluorometrically. Alternatively, GTPγS binding assays measure receptor-G protein coupling. These assays confirm the compound's agonist activity at the motilin receptor.
|
| Animal Protocol |
In vivo animal studies for EM-523 utilize models of gastrointestinal motility, such as gastric emptying assays or intestinal transit studies in rodents. The compound is administered orally or intravenously. Gastrointestinal motility is assessed by measuring the passage of a radioactive or fluorescent marker through the GI tract. Contractions of the duodenum or stomach are measured using strain gauge transducers or manometry. Efficacy is compared to vehicle and reference prokinetic agents (e.g., erythromycin, motilin).
|
| ADME/Pharmacokinetics |
EM-523 has molecular weight of 715.9 g/mol (C₃₇H₆₅NO₁₂). As a macrolide derivative, it has poor oral bioavailability due to acid sensitivity. The compound's pharmacokinetic properties are similar to erythromycin, with rapid metabolism and excretion. Its acid sensitivity is a limitation for oral administration. The compound is typically used in research settings and is not developed as a therapeutic drug.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity of EM-523 is not extensively documented. As a motilin receptor agonist, potential adverse effects may include gastrointestinal side effects such as nausea, abdominal cramping, and diarrhea, which are mechanism-based. The compound's lack of antibacterial activity reduces the risk of antibiotic-associated adverse effects. Standard toxicology studies would be required for therapeutic development. The compound is available for research purposes only.
|
| References |
[3]. [Effect of motilin agonist, EM-523 on gastrointestinal motility]. Nihon Geka Gakkai Zasshi. 1991 Sep;92(9):1208-11. Japanese. PubMed PMID: 1944188. |
| Additional Infomation |
Erythromycin is an enol ether aminoglycoside antibiotic.
EM-523 (Erythromycin A enol ether) is a potent motilin receptor agonist with IC50 of 3.40 nM. It is a degradation product of erythromycin A with no antibacterial activity. It stimulates gastrointestinal motility via motilin receptor activation. It is available for research purposes only. |
| Molecular Formula |
C38H67NO12
|
|---|---|
| Molecular Weight |
729.95
|
| Exact Mass |
715.451
|
| Elemental Analysis |
C, 62.53; H, 9.25; N, 1.92; O, 26.30
|
| CAS # |
33396-29-1
|
| PubChem CID |
83954
|
| Appearance |
Solid powder
|
| Density |
1.2g/cm3
|
| Boiling Point |
791.6ºC at 760mmHg
|
| Melting Point |
133-135ºC
|
| Flash Point |
432.6ºC
|
| Index of Refraction |
1.542
|
| LogP |
2.892
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
50
|
| Complexity |
1220
|
| Defined Atom Stereocenter Count |
17
|
| SMILES |
CC[C@@H]1[C@@]([C@@H]([C@H](C2=C(C[C@@](O2)([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]3C[C@@]([C@H]([C@@H](O3)C)O)(C)OC)C)O[C@H]4[C@@H]([C@H](C[C@H](O4)C)N(C)C)O)C)C)C)O)(C)O
|
| InChi Key |
UTTLXGDLSXWDJI-OTELOYJSSA-N
|
| InChi Code |
InChI=1S/C38H67NO12/c1-14-26-38(11,44)31(41)21(5)29-19(3)17-37(10,51-29)33(50-35-28(40)25(39(12)15-2)16-20(4)46-35)22(6)30(23(7)34(43)48-26)49-27-18-36(9,45-13)32(42)24(8)47-27/h20-28,30-33,35,40-42,44H,14-18H2,1-13H3/t20-,21+,22+,23-,24+,25+,26-,27+,28-,30+,31-,32+,33-,35+,36-,37+,38-/m1/s1
|
| Chemical Name |
(1S,2R,3S,4S,5R,8R,9S,10R,11R)-8-ethyl-2-[(2S,3R,4S,6R)-4-(ethyl-methylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-9,10-dihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-1,3,5,9,11,13-hexamethyl-7,15-dioxabicyclo[10.2.1]pentadec-12-en-6-one
|
| Synonyms |
Erythromycin A enol ether EM-523 EM 523 EM523.
|
| 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)
|
| 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
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 | 1.3700 mL | 6.8498 mL | 13.6996 mL | |
| 5 mM | 0.2740 mL | 1.3700 mL | 2.7399 mL | |
| 10 mM | 0.1370 mL | 0.6850 mL | 1.3700 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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