| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg | |||
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| Targets |
GSK726701A targets the prostaglandin E2 receptor 4 (EP4), a G protein-coupled receptor involved in inflammation and pain signaling. As a partial agonist, it binds to and activates the EP4 receptor with submaximal efficacy. Its high selectivity for EP4 over EP1-3 receptors makes it a valuable tool for studying EP4-mediated signaling.
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| ln Vitro |
GSK726701A exhibits no discernible activity against a wider variety of targets and is extremely selective (>100-fold) against a panel of additional prostaglandin receptors (EP1-3, DP1, FP, IP, TP). In a human whole blood (HWB) experiment, it showed EP4 agonist action with equal potency and intrinsic activity (pEC50=8.2), blocking LPS-mediated TNFα production [1].
In vitro, GSK726701A acts as a partial agonist of the EP4 receptor with a pEC₅₀ of 7.4. It shows high selectivity (>100-fold) against a set of other prostaglandin receptors (EP1-3). The compound's activity is assessed using receptor binding and functional assays to measure its potency and efficacy at the EP4 receptor. |
| ln Vivo |
There is strong pharmacokinetic evidence for GSK726701A in rats, dogs, and monkeys. Animal models of inflammatory and neuropathic pain are highly responsive to GSK726701A. At a dose of 3 mg/kg, which is comparable to the clinical gold standard of 30 mg/kg gabapentin, GSK726701A totally reverses mechanical allodynia caused by CCI. In the FCA acute inflammatory pain rat model, GSK726701A has an ED50 of 0.2 mg/kg[1].
In vivo, GSK726701A exhibits robust efficacy in various animal models for both inflammatory and neuropathic pain. It demonstrates time-dependent mechanical allodynia at a dosage of 3 mg/kg, matching the efficacy of gabapentin administered at 30 mg/kg. These results suggest potent analgesic activity in preclinical pain models. |
| Enzyme Assay |
In vitro receptor binding assays for GSK726701A are performed using membrane preparations expressing human EP4 and other prostaglandin receptors. Radioligand competition binding assays are used to measure the compound's affinity and selectivity for EP4. Functional assays measure EP4-mediated cAMP accumulation to determine the compound's partial agonist activity and pEC₅₀.
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| Cell Assay |
In vitro cellular assays for GSK726701A are performed using cells expressing human EP4 receptors. Cells are treated with the compound, and cAMP accumulation is measured using ELISA or HTRF assays. The pEC₅₀ value (7.4) is calculated from concentration-response curves. Selectivity is assessed by testing the compound against other prostaglandin receptors (EP1-3).
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| Animal Protocol |
In vivo animal experiments for GSK726701A are conducted in rodent models of inflammatory and neuropathic pain. A typical protocol involves administration of the compound (e.g., 3 mg/kg) to rats or mice, followed by assessment of mechanical allodynia using von Frey filaments. Efficacy is compared to reference compounds such as gabapentin (30 mg/kg).
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of GSK726701A have been characterized in preclinical studies. The compound has a molecular weight of 423.43 and molecular formula C₂₄H₂₂FNO₅. It is supplied as a research compound. Further PK details, including half-life, bioavailability, and tissue distribution, would be available from the manufacturer's data sheets.
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| Toxicity/Toxicokinetics |
Toxicological data for GSK726701A are not extensively reported in the available literature. As a research-use compound, its safety profile has not been formally evaluated in comprehensive preclinical toxicology studies. The compound is intended for research purposes only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
GSK726701A is a novel EP4 receptor partial agonist with CAS number 945721-87-9, molecular formula C₂₄H₂₂FNO₅, and molecular weight 423.43. It has a pEC₅₀ of 7.4 and shows >100-fold selectivity over EP1-3 receptors. It exhibits robust efficacy in inflammatory and neuropathic pain models at 3 mg/kg. This product is for research use only.
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| Molecular Formula |
C24H22FNO5
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|---|---|
| Molecular Weight |
423.43359041214
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| Exact Mass |
423.148
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| CAS # |
945721-87-9
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| PubChem CID |
16678098
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| Appearance |
White to off-white solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
660
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CC1C(F)=CC(N2CC3C(=C(C4C(C=3OCC)=CC=CC=4)OCC)C2=O)=CC=1)O
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| InChi Key |
YJEFCZJZEASKIO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H22FNO5/c1-3-30-22-16-7-5-6-8-17(16)23(31-4-2)21-18(22)13-26(24(21)29)15-10-9-14(11-20(27)28)19(25)12-15/h5-10,12H,3-4,11,13H2,1-2H3,(H,27,28)
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| Chemical Name |
2-[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-2-fluorophenyl]acetic 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) |
DMSO : ~25 mg/mL (~59.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3617 mL | 11.8083 mL | 23.6167 mL | |
| 5 mM | 0.4723 mL | 2.3617 mL | 4.7233 mL | |
| 10 mM | 0.2362 mL | 1.1808 mL | 2.3617 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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