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| 10mg |
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| Targets |
EP2 receptor antagonist-1 specifically targets the prostaglandin E2 receptor subtype EP2, a GPCR. It exhibits a novel mechanism of action as an allosteric antagonist, meaning it binds to a site distinct from the orthosteric (PGE2 binding) site and its inhibitory effect depends on the presence of the agonist. This makes it a “neutral” allosteric antagonist.
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| ln Vitro |
EP2 receptor antagonist-1 is a potent EP2 antagonist. By blocking EP2 activity, it displays anti-inflammatory effects in relevant in vitro assays. The activity is reversible, distinguishing it from irreversible inhibitors. The specific IC50 or Kd values are not publicly defined, but it is described as a "potent" binder that functions in an agonist-dependent manner.
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| ln Vivo |
In in vivo models, EP2 receptor antagonist-1 has shown anti-inflammatory effects, although specific model data is limited. Given its mechanism, it is hypothesized to reduce PGE2-mediated inflammation, including vasodilation and pain sensitization. It may also inhibit EP2-mediated tumor progression and neurodegenerative processes where EP2 signaling is pathogenic.
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| Enzyme Assay |
The specific binding protocol for evaluating an allosteric ligand is more complex than simple competitive binding. A radioligand binding assay with [3H]-PGE2 is performed in the presence of varying concentrations of EP2 receptor antagonist-1, and also in the presence of an orthosteric agonist (like PGE2). The “agonist-dependence” is confirmed by comparing binding curves in the presence and absence of the endogenous agonist. Data must be analyzed using an allosteric ternary complex model (e.g., operational model of allosterism) rather than standard competitive binding equations.
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| Cell Assay |
In an in vitro cell-based assay, HEK-293 cells co-expressing the EP2 receptor and a CRE-luciferase reporter are used. Cells are pre-incubated with EP2 receptor antagonist-1 (0.1-10,000 nM) for 30 minutes, and then stimulated with a fixed concentration of PGE2 (EC80). Following 4-6 hours of incubation, luciferase activity (a measure of cAMP accumulation) is measured. Reversibility is confirmed by performing a washout experiment: cells are incubated with the antagonist, washed, and then re-stimulated with PGE2 to see if inhibition persists.
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| Animal Protocol |
A typical in vivo protocol for evaluating an EP2 antagonist uses a rodent model of acute inflammation. Male CD-1 mice receive an intraplantar injection of carrageenan (1%) into the hind paw to induce edema and hyperalgesia. EP2 receptor antagonist-1 is administered at doses of 1-30 mg/kg, 30-60 minutes prior to or 2 hours post-carrageenan injection. Paw edema is measured using a plethysmometer, and mechanical allodynia is measured using von Frey filaments. Myeloperoxidase (MPO) activity in the paw tissue can also be measured to quantify neutrophil infiltration.
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| ADME/Pharmacokinetics |
Published pharmacokinetic data for EP2 receptor antagonist-1 is not available. As a small molecule designed for standard in vivo administration, it is expected to have properties suitable for parenteral (IP/IV) or oral delivery. To confirm target engagement in vivo, a PK/PD study would be required to correlate plasma concentration with the inhibition of PGE2-induced cAMP production.
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| Toxicity/Toxicokinetics |
Specific toxicology data for EP2 receptor antagonist-1 is not available in published literature. As a research chemical, potential toxicities would be assessed in the context of the animal models used. Because EP2 receptors are expressed widely (kidney, uterus, lung, vasculature), long-term antagonism could potentially affect blood pressure regulation (renin release) or reproductive function (parturition).
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| References | |
| Additional Infomation |
EP2 receptor antagonist-1 is a unique pharmacological tool due to its allosteric binding mode. Most prostanoid antagonists are orthosteric (competitive). Allosteric antagonists offer potential advantages, including high subtype selectivity and the ability to fine-tune receptor signaling rather than completely shutting it down. This compound is not an FDA-approved drug and is for research use only. It is a valuable tool for dissecting EP2 receptor biology.
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| Molecular Formula |
C24H22N4O5
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| Molecular Weight |
446.46
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| Exact Mass |
446.159
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| CAS # |
848920-08-1
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| PubChem CID |
664888
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
712
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(OC1)COC(=O)C2=C(N(C3=NC4=CC=CC=C4N=C23)C5=CC6=C(C=C5)OCCO6)N
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| InChi Key |
OHXALKVNKANGKL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H22N4O5/c25-22-20(24(29)33-13-15-4-3-9-30-15)21-23(27-17-6-2-1-5-16(17)26-21)28(22)14-7-8-18-19(12-14)32-11-10-31-18/h1-2,5-8,12,15H,3-4,9-11,13,25H2
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| Chemical Name |
oxolan-2-ylmethyl 2-amino-1-(2,3-dihydro-1,4-benzodioxin-6-yl)pyrrolo[3,2-b]quinoxaline-3-carboxylate
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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) |
DMSO: 100 mg/mL (223.98 mM)
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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 | 2.2398 mL | 11.1992 mL | 22.3984 mL | |
| 5 mM | 0.4480 mL | 2.2398 mL | 4.4797 mL | |
| 10 mM | 0.2240 mL | 1.1199 mL | 2.2398 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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