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| Targets |
EP4 receptor antagonist 1 targets the prostaglandin E2 receptor 4 (EP4), a G protein-coupled receptor implicated in inflammation, cancer progression, pain signaling, and autoimmune disorders. It acts as a competitive antagonist, blocking the binding of prostaglandin E2 to the EP4 receptor. By inhibiting EP4, it reverses PGE2-induced immunosuppression in the tumor microenvironment.
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| ln Vitro |
In CHO-Gα16 cells overexpressing human EP4 receptor, EP4 receptor antagonist 1 (compound 59) antagonized human EP4 with an IC50 of 6.1 ± 0.2 nM in the calcium flux assay. With an IC50 of 16.2±1.7 nM, EP4 receptor antagonist 1 antagonized human EP4 in the calcium flux experiment in CHO-Gα16 cells overexpressing the mouse EP4 receptor [1]. With an IC50 of 18.7±0.6 nM, EP4 receptor antagonist 1 dose-dependently prevents PGE2-stimulated cAMP buildup in HEK293-EP4 cells. With an IC50 of 5.2±0.4 nM, EP4 receptor antagonist 1 dose-dependently suppresses the expression of the CRE reporter gene in HEK293 cells. With an IC50 of 0.4±0.1nM, EP4 receptor antagonist 1 dose-dependently blocks PGE2-stimulated β-arrestin recruitment in HEK293-EP4 cells [1]. In a concentration-dependent manner, EP4 receptor antagonist 1 (1 nM-10 μM) reverses PGE2-induced ERK phosphorylation [1].
In vitro, EP4 receptor antagonist 1 potently inhibits human and mouse EP4 receptors with IC50 values of 6.1 nM and 16.2 nM, respectively. It shows IC50 values >10 μM for human EP1, EP2, and EP3 receptors, demonstrating high selectivity. The compound reverses PGE2-induced signaling at concentrations of 1 nM-10 μM. |
| ln Vivo |
In BALB/c female mice, the oral administration of EP4 receptor antagonist 1 (16, 50, and 150 mg/kg; once daily for two weeks) greatly prevented the formation of tumors. Not a single mouse group showed any discernible weight loss. Mice respond well to EP4 receptor antagonist 1 at the tested doses [1]. In mice, EP4 receptor antagonist 1 (1 mg/kg; intraperitoneal) had a good half-life (t1/2) of 4.1 hours and moderate clearance (CL=1.7 L/h/kg). In mice, EP4 receptor antagonist 1 (5 mg/kg; oral) exhibits high bioavailability (F=48.0%) and a 4.7-hour half-life (t1/2).
In vivo, EP4 receptor antagonist 1 is well tolerated in mice at the tested dosage. As a selective EP4 antagonist, it can be administered to animal models of cancer to study the role of EP4 in tumor immunity. By reversing PGE2-induced immunosuppression, it may enhance anti-tumor immune responses. The compound is being investigated for cancer immunotherapy. |
| Enzyme Assay |
In vitro receptor binding assays for EP4 receptor antagonist 1 involve measuring its affinity for EP4, EP1, EP2, and EP3 receptors. Radioligand binding studies using ³H-PGE2 or other prostanoid ligands are performed on membranes from cells expressing the receptors. IC50 values of 6.1 nM for human EP4 and 16.2 nM for mouse EP4 are determined. Selectivity is confirmed by testing against other EP receptors.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: CHO-EP4 Cell Tested Concentrations: 1 nM, 100 nM, 10 μM Incubation Duration: 20 minutes pretreatment, followed by 30 nM PGE2 simulation for 10 minutes. Experimental Results: PGE2-induced ERK phosphorylation was reversed in a concentration-dependent manner. For in vitro cell-based assays, cells expressing EP4 receptors are cultured and treated with EP4 receptor antagonist 1 at various concentrations. Receptor antagonism is confirmed by its ability to block PGE2-induced cAMP accumulation or other downstream signaling pathways. Cell viability is assessed by standard assays. The compound's effects on immune cell function can be assessed in co-culture systems. |
| Animal Protocol |
Animal/Disease Models: BALB/c female mouse (6 weeks old) CT26 colon cancer model [1]
Doses: 16, 50, 150 mg/kg Route of Administration: oral; one time/day for two weeks Experimental Results: Tumor growth inhibition (TGI ) is 24.6% at 16 mg/kg, 54.7% at 50 mg/kg, and 63.8% at 150 mg/kg. Animal/Disease Models: BALB/c female mice [1] Doses: 1 mg/kg and 5 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)or po (po (oral gavage)) dose 1 mg/kg (5 mL/kg ) and 5 mg/kg (10 ml/kg), respectively. Experimental Results: At a dose of 1 mg/kg (iv), mice demonstrated moderate clearance (CL=1.7 L/h/kg) with a corresponding favorable half-life (t1/2) of 4.1 hrs (hrs (hours)). demonstrated good bioavailability in mice (F = 48.0%) with a corresponding favorable half-life (t1/2) of 4.7 hrs (hrs (hours)) at a dose of 5 mg/kg (oral). In vivo animal studies with EP4 receptor antagonist 1 are conducted in models of cancer immunotherapy. Tumor-bearing mice are treated with the compound orally or intraperitoneally at doses determined from pharmacokinetic studies. Tumor growth inhibition and immune cell infiltration are monitored. The compound's ability to enhance anti-tumor immune responses is assessed. The compound is well tolerated in mice at the tested dosage. |
| ADME/Pharmacokinetics |
EP4 receptor antagonist 1 (CAS: 2287259-07-6) has a molecular weight of 458.43 g/mol and a molecular formula of C23H21F3N4O3. Chemical name: 4-[(1S)-1-({4-[(1E)-prop-1-en-1-yl]-1-{[4-(trifluoromethyl)phenyl]methyl}-1H-1,2,3-triazol-5-yl}formamido)ethyl]benzoic acid. Appearance: solid powder. Purity: ≥98%. Storage: -20°C.
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| Toxicity/Toxicokinetics |
EP4 receptor antagonist 1 is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile and is well tolerated in mice at the tested dosage. As an EP4 antagonist, it may have effects on inflammation and immune function. The compound's high selectivity for EP4 over other EP receptors may reduce off-target effects. Standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
EP4 receptor antagonist 1 is a highly potent and selective competitive prostanoid EP4 receptor antagonist with IC50 values of 6.1 nM and 16.2 nM for human and mouse EP4, respectively. It shows IC50 values >10 μM for human EP1, EP2, and EP3. It is effective for cancer immunotherapy research. It has a molecular weight of 458.43 g/mol and a molecular formula of C23H21F3N4O3. It is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C23H21F3N4O3
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| Molecular Weight |
458.433055639267
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| Exact Mass |
458.156
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| CAS # |
2287259-07-6
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| PubChem CID |
146014480
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| Appearance |
White to off-white solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
702
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC(C1C=CC(=CC=1)CN1C(=C(/C=C/C)N=N1)C(N[C@@H](C)C1C=CC(C(=O)O)=CC=1)=O)(F)F
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| InChi Key |
ZTWUZRMXAVDXJV-XGACYXMMSA-N
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| InChi Code |
InChI=1S/C23H21F3N4O3/c1-3-4-19-20(21(31)27-14(2)16-7-9-17(10-8-16)22(32)33)30(29-28-19)13-15-5-11-18(12-6-15)23(24,25)26/h3-12,14H,13H2,1-2H3,(H,27,31)(H,32,33)/b4-3+/t14-/m0/s1
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| Chemical Name |
4-[(1S)-1-[[5-[(E)-prop-1-enyl]-3-[[4-(trifluoromethyl)phenyl]methyl]triazole-4-carbonyl]amino]ethyl]benzoic acid
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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 | 2.1814 mL | 10.9068 mL | 21.8136 mL | |
| 5 mM | 0.4363 mL | 2.1814 mL | 4.3627 mL | |
| 10 mM | 0.2181 mL | 1.0907 mL | 2.1814 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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