| Size | Price | Stock | Qty |
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| 10mg |
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| Other Sizes |
| Targets |
Prostanoid EP₄ receptor (antagonist; pKᵢ = 7.9 at human recombinant EP₄; pKB = 7.6 at human recombinant EP₄ in functional assay; pKB = 7.8 at native EP₄ in human middle cerebral artery; pKB = 7.6 at native EP₄ in human middle meningeal artery) [1]
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| ln Vitro |
In radioligand binding studies using membranes from HEK-293 EBNA cells expressing human recombinant EP₄ receptors, BGC20-1531 displaced [³H]-PGE₂ with a pKᵢ of 7.9. It exhibited negligible affinity (pKᵢ < 5) for human recombinant EP₁, EP₂, EP₃, TP, DP, and IP receptors. At a concentration of 10 μM, it caused less than 50% inhibition at a wide range of other 7TM receptors, ion channels, transporters, and enzymes. [1]
In HEK-293 EBNA cells stably expressing the human EP₄ receptor, BGC20-1531 (0.1, 1.0, 10 μM) caused a surmountable, competitive antagonism of PGE₂-stimulated cAMP accumulation. Schild analysis yielded an estimated pKB of 7.6. BGC20-1531 had no effect on forskolin-stimulated cAMP accumulation, indicating it is a specific antagonist. [1] In isolated rings of human middle cerebral artery pre-contracted with phenylephrine, BGC20-1531 (0.03-1 μM) competitively antagonized PGE₂-induced vasorelaxation with a pKB of 7.8. It also rapidly and completely reversed an established PGE₂-mediated relaxation. [1] In isolated rings of human middle meningeal artery pre-contracted with phenylephrine, BGC20-1531 (0.1-10 μM) competitively antagonized PGE₂-induced vasorelaxation with a pKB of 7.6. It also rapidly reversed an established PGE₂-mediated relaxation. [1] In isolated rings of human coronary, pulmonary, and renal arteries, where PGE₂ causes vasoconstriction, BGC20-1531 (1 μM) had no effect on basal tone and did not antagonize PGE₂-induced contractions. [1] In isolated rings of canine middle meningeal artery pre-contracted with phenylephrine, BGC20-1531 (0.1, 0.3, 1 μM) competitively antagonized PGE₂-induced relaxation with a mean pA₂ of 7.7. [1] |
| ln Vivo |
In anaesthetized beagle dogs, intra-arterial injection of PGE₂ (0.04 μg·kg⁻¹) increased carotid blood flow and decreased carotid resistance. Intravenous administration of BGC20-1531 (1, 3, 10 mg·kg⁻¹) caused a dose-dependent antagonism of these PGE₂-induced haemodynamic changes, with an ID₅₀ of 5 mg·kg⁻¹. The degree of antagonism correlated with the plasma concentration of the drug. BGC20-1531 had no effect on mean arterial pressure or heart rate. [1]
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| Enzyme Assay |
Broad-spectrum specificity screening was conducted against a panel of 42 7TM receptors, 9 transmitter-gated channels, 8 ion channels, 4 nuclear receptors, 5 cell-surface transporters, and 16 enzymes. At a concentration of 10 μM, BGC20-1531 caused less than 50% inhibition of binding or activity at all these targets, corresponding to a pKi < 5. [1]
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| Cell Assay |
cAMP Accumulation Assay: HEK-293 EBNA cells stably expressing the human EP₄ receptor were cultured in 96-well plates. Cells were pre-incubated with BGC20-1531 (0.1, 1.0, 10 μM) or vehicle for 60 minutes in the presence of IBMX, then stimulated with PGE₂ (0.0001-10 μM) for 15 minutes. The reaction was terminated with HCl. cAMP levels were measured by a competitive binding assay using [³H]-cAMP and a cAMP binding protein. [1]
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| Animal Protocol |
In Vivo Canine Carotid Haemodynamics:** Four beagle dogs were anaesthetized. The left common carotid artery was instrumented with a flow probe to measure carotid blood flow. A side branch was cannulated for intra-arterial PGE₂ injection. The femoral artery and vein were cannulated for blood pressure measurement and drug administration, respectively. Baseline responses to intra-arterial PGE₂ (0.04 μg·kg⁻¹) were established. BGC20-1531 (1, 3, and 10 mg·kg⁻¹) or vehicle was then administered intravenously as a slow bolus. The PGE₂ challenge was repeated 15 minutes after each dose. Blood samples were taken for plasma drug concentration analysis by LC-MS. [1]
In Vivo Canine Carotid Haemodynamics: Four beagle dogs were anaesthetized. The left common carotid artery was instrumented with a flow probe to measure carotid blood flow. A side branch was cannulated for intra-arterial PGE₂ injection. The femoral artery and vein were cannulated for blood pressure measurement and drug administration, respectively. Baseline responses to intra-arterial PGE₂ (0.04 μg·kg⁻¹) were established. BGC20-1531 (1, 3, and 10 mg·kg⁻¹) or vehicle was then administered intravenously as a slow bolus. The PGE₂ challenge was repeated 15 minutes after each dose. Blood samples were taken for plasma drug concentration analysis by LC-MS. [1] |
| ADME/Pharmacokinetics |
Following intravenous administration of BGC20-1531 (1, 3, and 10 mg·kg⁻¹) to dogs, there was a correlation between the plasma concentration of the drug and its pharmacodynamic effect (antagonism of PGE₂-induced carotid vasodilatation). [1]
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| References | |
| Additional Infomation |
BGC20-1531 (N-(4-[4-(5-methoxypyridin-2-yl)phenoxymethyl]-5-methylfuran-2-carbonyl)-2-methylbenzenesulphonamide sodium salt) is a novel, potent, and selective small molecule antagonist of the prostanoid EP₄ receptor. It was developed as a potential new treatment for migraine headache, based on the rationale that EP₄ receptors mediate cerebral vasodilatation and neuronal sensitization, which contribute to migraine pain. [1]
In vitro, BGC20-1531 acts as a competitive antagonist at human recombinant and native EP₄ receptors in cerebral and meningeal arteries. It can both prevent and reverse PGE₂-induced vasorelaxation. Unlike triptans, it does not constrict or affect PGE₂ responses in coronary, pulmonary, or renal arteries, suggesting a potential for a better cardiovascular safety profile. [1] In vivo, BGC20-1531 demonstrates dose-dependent efficacy in a canine model of carotid vasodilatation, a pharmacodynamic model relevant to migraine. The compound is highly selective for the EP₄ receptor over a wide range of other molecular targets. At the time of publication, BGC20-1531 was in clinical development for the treatment of migraine headache. [1] |
| Molecular Formula |
C26H25CLN2O6S
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|---|---|
| Molecular Weight |
529.004
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| Exact Mass |
528.112
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| CAS # |
1962928-26-2
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| Related CAS # |
BGC-20-1531 free base;736183-35-0
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| PubChem CID |
121513858
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
36
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| Complexity |
794
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C(C1=CC(COC2C=CC(C3C=CC(OC)=CN=3)=CC=2)=C(C)O1)NS(C1C(C)=CC=CC=1)(=O)=O
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| InChi Key |
ZSHYZCXOFPPBMH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H24N2O6S.ClH/c1-17-6-4-5-7-25(17)35(30,31)28-26(29)24-14-20(18(2)34-24)16-33-21-10-8-19(9-11-21)23-13-12-22(32-3)15-27-23;/h4-15H,16H2,1-3H3,(H,28,29);1H
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| Chemical Name |
4-[[4-(5-methoxypyridin-2-yl)phenoxy]methyl]-5-methyl-N-(2-methylphenyl)sulfonylfuran-2-carboxamide;hydrochloride
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| Synonyms |
BGC20-1531 HCl BGC20-1531 BGC-201531 PGN 1531 PGN-1531BGC 20-1531 BGC-20-1531BGC20-1531 hydrochloride BGC201531 BGC 201531 PGN1531
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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 | 1.8904 mL | 9.4518 mL | 18.9036 mL | |
| 5 mM | 0.3781 mL | 1.8904 mL | 3.7807 mL | |
| 10 mM | 0.1890 mL | 0.9452 mL | 1.8904 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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