| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 189 nM (GPR4)[1].
Targets GPR4, a proton-sensing G protein-coupled receptor that is activated by a decrease in extracellular pH. GPR4 antagonist 1 acts as an inhibitor, blocking receptor activation. This is characterized by its IC50 of 189 nM, which measures the concentration required to inhibit 50% of GPR4‘s activity in an in vitro assay. |
|---|---|
| ln Vitro |
By blocking GPR4, this antagonist is expected to inhibit the downstream signaling pathways activated by acidic pH. These pathways typically involve Gs, Gi, and Gq proteins, leading to increased cAMP production, calcium mobilization, and activation of transcription factors like NF-kappaB. In vitro, at its IC50, it would effectively neutralize GPR4-dependent inflammatory and cell survival signals.
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| ln Vivo |
Detailed in vivo activity data for GPR4 antagonist 1 is not publicly available. As a small molecule antagonist of a pH-sensing receptor, it has potential applications in animal models of inflammatory diseases (e.g., inflammatory bowel disease, arthritis), ischemic injury, and cancer, where tissue acidosis is a common feature and GPR4 may play a pathogenic role.
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| Enzyme Assay |
Cell-free radioligand binding assays for GPR4 are performed using membranes from cells that overexpress the human GPR4 receptor. The membranes are incubated with a fixed concentration of a radiolabeled agonist specific for GPR4 and increasing concentrations of GPR4 antagonist 1. Bound radioactivity is separated and counted to determine the IC50 (189 nM).
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| Cell Assay |
Functional cell-based assays for GPR4 antagonism typically measure the inhibition of pH-induced cAMP accumulation. Cells (e.g., HEK293) expressing GPR4 are loaded with a fluorescent cAMP biosensor or pre-incubated with the antagonist before being exposed to an acidic medium (e.g., pH 6.8). The ability of the antagonist to block the increase in intracellular cAMP is measured, confirming its functional activity.
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| Animal Protocol |
No specific animal studies for GPR4 antagonist 1 are publicly reported. A potential in vivo model could be a mouse model of colitis induced by dextran sulfate sodium (DSS). GPR4 antagonist 1 could be administered orally or intraperitoneally daily. Endpoints would include disease activity index (body weight, stool consistency, bleeding), colon length, and histological scoring of inflammation.
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| ADME/Pharmacokinetics |
Detailed PK data for GPR4 antagonist 1 is not publicly available. As a small molecule with a molecular weight of 431.62 and a molecular formula of C27H37N5, it may be suitable for oral administration. It is soluble in DMSO (125 mg/mL), but its formulation for in vivo use and its ADME properties have not been reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for GPR4 antagonist 1. As a research-grade antagonist, no safety studies have been published. It is likely to be well-tolerated, but the pharmacological effects of blocking GPR4, a key pH sensor in immune and vascular cells, could potentially influence normal homeostatic processes and inflammatory responses.
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| References | |
| Additional Infomation |
GPR4 antagonist 1 is a research chemical and is not approved for clinical use. It represents a valuable tool compound for exploring the role of pH-sensing GPCRs in disease. GPR4 has emerged as a potential drug target for inflammatory bowel disease, cancer, and ischemic conditions, and this antagonist can help validate its role.
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| Molecular Formula |
C27H37N5
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|---|---|
| Molecular Weight |
431.62
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| Exact Mass |
431.305
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| CAS # |
1197879-16-5
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| PubChem CID |
57970302
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| Appearance |
Light yellow to yellow ointment
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| LogP |
4.573
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
591
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])N(C([H])([H])/C(/[H])=C(\[H])/C2C([H])=C([H])C(=C([H])C=2[H])C([H])([H])N2C(C([H])([H])C([H])([H])[H])=NC3C(C([H])([H])[H])=C([H])C(C([H])([H])[H])=NC2=3)C([H])([H])C1([H])[H]
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| InChi Key |
UAMIBPKKKLTAKG-BQYQJAHWSA-N
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| InChi Code |
InChI=1S/C27H37N5/c1-6-25-29-26-21(4)18-22(5)28-27(26)32(25)19-24-11-9-23(10-12-24)8-7-13-30-14-16-31(17-15-30)20(2)3/h7-12,18,20H,6,13-17,19H2,1-5H3/b8-7+
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| Chemical Name |
2-ethyl-5,7-dimethyl-3-[[4-[(E)-3-(4-propan-2-ylpiperazin-1-yl)prop-1-enyl]phenyl]methyl]imidazo[4,5-b]pyridine
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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: 125 mg/mL (289.61 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (4.82 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3169 mL | 11.5843 mL | 23.1685 mL | |
| 5 mM | 0.4634 mL | 2.3169 mL | 4.6337 mL | |
| 10 mM | 0.2317 mL | 1.1584 mL | 2.3169 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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