| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
| Targets |
EMA400 selectively antagonizes the angiotensin II type 2 receptor (AT2R), a G protein-coupled receptor that counteracts AT1R-mediated effects. AT2R is expressed in sensory neurons and is involved in neuropathic pain signaling. By blocking AT2R, EMA400 alleviates pain-like behavior in rodent models. The S-enantiomer EMA401 has the highest binding specificity at both rat and human AT2 receptors (>10,000).
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|---|---|
| ln Vitro |
In vitro, EMA400 has >30,000-fold binding selectivity for AT2R over AT1R. It is a racemic mixture, and the S-enantiomer EMA401 has >10,000-fold binding specificity at both rat and human AT2 receptors. EMA400 and EMA401 show high binding affinity for the AT2 receptor.
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| ln Vivo |
In vivo, single intraperitoneal doses of EMA400 evoke dose-dependent relief of mechanical allodynia in rats with chronic constriction injury of the sciatic nerve. The mean ED50 for EMA400 is 0.013 mg/kg, compared to 3.22 and 0.78 mg/kg for EMA200 and EMA300, respectively. Oral EMA401 (10 mg/kg) given as a single dose or once-daily for 7 days alleviates thermal hyperalgesia in CCI rats.
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| Enzyme Assay |
AT2R binding assays use membranes from cells expressing recombinant AT2R and radiolabeled angiotensin II or a selective AT2R antagonist. EMA400 is serially diluted and incubated with membranes. Bound radioactivity is measured by rapid filtration. Binding selectivity for AT2R over AT1R is determined.
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| Cell Assay |
For pain behavioral assays, rats with chronic constriction injury of the sciatic nerve are used. EMA400 is administered intraperitoneally or orally. Mechanical allodynia is assessed using von Frey filaments. Thermal hyperalgesia is assessed using the Hargreaves test.
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| Animal Protocol |
Rodent models of neuropathic pain include chronic constriction injury (CCI) of the sciatic nerve in rats. EMA400 is administered intraperitoneally at doses of 0.003-0.03 mg/kg. Mechanical allodynia and thermal hyperalgesia are assessed.
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| References |
Anand U, Yiangou Y, Sinisi M, Fox M, MacQuillan A, Quick T, Korchev YE, Bountra C, McCarthy T, Anand P. Mechanisms underlying clinical efficacy of Angiotensin II type 2 receptor (AT2R) antagonist EMA401 in neuropathic pain: clinical tissue and in vitro studies. Mol Pain. 2015 Jun 26;138. doi: 10.1186/s12990-015-0038-x. PubMed PMID: 26111701; PubMed Central PMCID: PMC4482278.
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| Molecular Formula |
C32H29NO5
|
|---|---|
| Molecular Weight |
507.5764
|
| Exact Mass |
507.204
|
| CAS # |
152362-51-1
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| Related CAS # |
152362-51-1;
|
| PubChem CID |
9892451
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
5.6
|
| tPSA |
76.1
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
38
|
| Complexity |
752
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])C1=C(C([H])=C([H])C2=C1C([H])([H])C([H])(C(=O)O[H])N(C(C([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O)C2([H])[H])OC([H])([H])[H]
|
| InChi Key |
GHBCIXGRCZIPNQ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C32H29NO5/c1-37-28-18-17-25-20-33(31(34)29(23-13-7-3-8-14-23)24-15-9-4-10-16-24)27(32(35)36)19-26(25)30(28)38-21-22-11-5-2-6-12-22/h2-18,27,29H,19-21H2,1H3,(H,35,36)
|
| Chemical Name |
5-Benzyloxy-2-diphenylacetyl-6-methoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid
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| Synonyms |
EMA400 EMA 400 EMA-400 PD-126055 PD126055 PD 126055
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| 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 | 1.9701 mL | 9.8507 mL | 19.7013 mL | |
| 5 mM | 0.3940 mL | 1.9701 mL | 3.9403 mL | |
| 10 mM | 0.1970 mL | 0.9851 mL | 1.9701 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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