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| Targets |
L-826266 targets the prostaglandin E2 (PGE2) receptor subtype EP3, a G protein-coupled receptor that mediates the effects of PGE2. EP3 receptors are widely expressed in various tissues and are involved in diverse physiological processes, including inflammation, pain, fever, and regulation of smooth muscle tone. L-826266 is a potent and selective competitive antagonist of the EP3 receptor, with a Ki of 0.8 nM. It also binds to the EP4 receptor with lower affinity (Ki = 715 nM) but does not bind to EP1 or EP2 receptors up to a concentration of 5,000 nM. By blocking EP3 receptors, L-826266 inhibits PGE2-mediated signaling, which can modulate inflammatory and immune responses, reduce pain, and affect vascular tone.
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| ln Vitro |
L-826266 (1 μM) inhibits the PGE2-induced reduction in Na+,K+-ATPase activity in adult rat hippocampus slices [2].
In vitro studies have characterized L-826266 as a potent and selective EP3 receptor antagonist. In receptor binding assays, it has a Ki of 0.8 nM for the EP3 receptor, 715 nM for the EP4 receptor, and no significant binding to EP1 or EP2 receptors up to 5,000 nM. In functional assays, L-826266 inhibits vasoconstriction induced by the EP3 agonist sulprostone in isolated human pulmonary arteries in a concentration-dependent manner, with EC50 values ranging from 0.45 to 24.5 µM. It also inhibits sulprostone-induced norepinephrine and serotonin release in rat cortex and norepinephrine release in rat vas deferens, with pA2 values of 7.56, 7.67, and 7.87, respectively. These findings confirm that L-826266 is a potent antagonist of EP3 receptor-mediated responses. |
| ln Vivo |
PTZ-induced clonic and generalized tonic-clonic seizures exhibit delayed seizure start and increased latency when treated with L-826266 (0.01-1 nmol/site; icv; once) [1].
In vivo studies have demonstrated that L-826266 has effects on seizure activity. In a pentylenetetrazole (PTZ)-induced seizure model, intracerebroventricular (icv) administration of L-826266 at doses of 0.01-1 nmol/site delayed seizure start and increased latency for clonic and generalized tonic-clonic seizures. These findings suggest that EP3 receptor antagonism may modulate neuronal excitability and seizure susceptibility. However, specific in vivo protocols and results are not extensively detailed in the available literature. L-826266 is used as a research tool to study the role of EP3 receptors in various physiological and pathological processes. |
| Enzyme Assay |
The in vitro receptor binding assays for L-826266 measure its affinity for the EP3 receptor. In a typical assay, membranes are prepared from cells expressing the human EP3 receptor and incubated with a radiolabeled ligand that binds to the EP3 receptor, such as [3H]PGE2. Increasing concentrations of unlabeled L-826266 are added to compete with the radiolabeled ligand for binding. After incubation, the bound and free ligand are separated by filtration, and the radioactivity is measured. The Ki is determined from the competition curve. For L-826266, the Ki for EP3 is 0.8 nM. To assess selectivity, the compound is tested against EP1, EP2, and EP4 receptors. Functional assays measure the compound's ability to inhibit EP3 agonist-induced responses, such as vasoconstriction or neurotransmitter release.
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| Cell Assay |
In vitro cell-based assays for L-826266 are used to study its effects on EP3 receptor-mediated signaling. A common assay involves measuring the inhibition of PGE2-induced intracellular signaling in cells expressing the EP3 receptor. For example, EP3 receptor activation can lead to inhibition of adenylyl cyclase and a decrease in cAMP levels. Cells are treated with PGE2 in the presence or absence of L-826266, and cAMP levels are measured using a competitive immunoassay. The compound's ability to reverse the PGE2-induced decrease in cAMP is assessed. Other functional assays measure the inhibition of EP3 agonist-induced calcium mobilization or other downstream signaling events. These cell-based assays confirm that L-826266 is a functional antagonist at the EP3 receptor.
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| Animal Protocol |
Animal/Disease Models: Adult male Wistar rats (250-300 g) were injected with pentylenetetrazole (PTZ) [1]
Doses: 0.01 nmol/site, 0.1 nmol/site or 1 nmol/site Route of Administration: icv; Experimental Results: Increased latency of PTZ-induced clonic and generalized tonic-clonic seizures. In vivo animal experiments for L-826266 have been conducted in seizure models. In a typical study, L-826266 is administered by intracerebroventricular (icv) injection at doses of 0.01-1 nmol/site. Seizures are then induced by administration of pentylenetetrazole (PTZ), and the latency to seizure onset and the severity of seizures are recorded. The compound's ability to delay seizure start and increase latency is assessed. Other in vivo models could include models of pain, inflammation, or vascular function, depending on the research question. However, specific protocols for L-826266 are not extensively detailed in the available literature. The compound's selectivity for EP3 over other EP receptors makes it a useful tool for studying EP3-mediated effects in vivo. |
| ADME/Pharmacokinetics |
L-826266 has a molecular weight of 570.9 g/mol and a molecular formula of C27H21BrClNO4S. It is a solid compound. For research use, L-826266 is typically supplied as a powder. It is soluble in DMSO at approximately 10 mg/mL (17.52 mM). For in vivo administration, it can be formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline (suspension) or in 10% DMSO + 90% corn oil (clear solution). For storage, it is recommended to keep the powder at -20°C for up to 3 years or at 4°C for up to 2 years. In solvent, it can be stored at -80°C for 6 months or at -20°C for 1 month. The compound is stable at ambient temperature for a few days during shipping.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for L-826266 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. In vivo studies have used doses of 0.01-1 nmol/site by icv injection without reported overt toxicity. However, comprehensive toxicological studies, including acute and chronic toxicity studies, have not been reported. As with all research chemicals, standard laboratory safety precautions should be followed when handling L-826266. Its use is limited to research applications and it is not intended for human or veterinary use.
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| References | |
| Additional Infomation |
L-826266 is a research compound and is not approved for any clinical or therapeutic use. It is a potent and selective competitive antagonist of the prostaglandin E2 receptor subtype EP3, with a Ki of 0.8 nM. L-826266 also binds to the EP4 receptor with a Ki of 715 nM but does not bind to EP1 or EP2 receptors up to a concentration of 5,000 nM. It inhibits vasoconstriction induced by the EP3 agonist sulprostone and inhibits sulprostone-induced neurotransmitter release. L-826266 has been shown to delay seizure start and increase latency in a PTZ-induced seizure model. The compound is used to study EP3 receptor-mediated signaling in inflammation, pain, and other physiological processes, and to validate EP3 as a therapeutic target for various diseases.
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| Molecular Formula |
C27H21BRCLNO4S
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| Molecular Weight |
570.88
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| Exact Mass |
569.006
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| CAS # |
244101-03-9
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| PubChem CID |
9808643
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.662
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| LogP |
8.29
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
847
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C(C=C1)Br)S(=O)(=O)NC(=O)/C=C/C2=C(C=CC(=C2)Cl)CC3=CC4=CC=CC=C4C=C3
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| InChi Key |
DYXFUJYHEDGCLS-UKTHLTGXSA-N
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| InChi Code |
InChI=1S/C27H21BrClNO4S/c1-34-25-12-10-23(28)17-26(25)35(32,33)30-27(31)13-9-22-16-24(29)11-8-21(22)15-18-6-7-19-4-2-3-5-20(19)14-18/h2-14,16-17H,15H2,1H3,(H,30,31)/b13-9+
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| Chemical Name |
(E)-N-(5-bromo-2-methoxyphenyl)sulfonyl-3-[5-chloro-2-(naphthalen-2-ylmethyl)phenyl]prop-2-enamide
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| Synonyms |
L-826266 L826266 L 826266
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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 : ~10 mg/mL (~17.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.67 mg/mL (2.93 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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: ≥ 1.67 mg/mL (2.93 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 16.7 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 | 1.7517 mL | 8.7584 mL | 17.5168 mL | |
| 5 mM | 0.3503 mL | 1.7517 mL | 3.5034 mL | |
| 10 mM | 0.1752 mL | 0.8758 mL | 1.7517 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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