BPN-37440
BPN-37440 is a blood-brain barrier-permeable, selective, and orally active EP2 receptor inhibitor with an IC50 of 53-60 nM. BPN-37440 inhibits the expression of inflammatory mediators IL-1β and COX-2, with an IC50 of 21 nM for IL-1β and 42 nM for COX-2. BPN-37440 reduces microgliosis in key brain regions of mice with pilocarpine (HY-B0726A)-induced status epilepticus and reverses their working memory and recognition memory deficits. BPN-37440 can be used for research on status epilepticus.
For research use only. We do not sell to patients.
- CAS No.: 3120759-70-5
- Formula: C21H22N4O
- Molecular Weight:346.43
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
EP2 53-60 nM (IC50) |
IL-1β 21 nM (IC50) |
COX-2 42 nM (IC50) |
In Vitro
BPN-37440 (0.01-10000 nM) potently and selectively inhibits the EP2 receptor in C6 glioma cells, with an IC50 of 53-60 nM[1].
BPN-37440 (30-1000 nM) acts as an inhibitor of the hEP2 receptor (KB = 5.65 nM) and mouse EP2 receptor (KB = 9.55 nM) in C6 glioma cells[1].
BPN-37440 (0-1000 nM; 30 min preincubation, 2 h stimulation) potently inhibits the expression of inflammatory mediators induced by LPS/EP2 agonists in BV2-hEP2 microglia, with an IC50 of 21 nM for IL-1β and 42 nM for COX-2[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:BV2 microglial cells overexpressing human EP2 receptors (BV2-hEP2)
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Concentration:0-1000 nM
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Incubation Time:30 min (preincubation); 2 h (stimulation)
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Result:Significantly attenuated the LPS/CP544326-induced upregulation of COX-2, IL-6, and IL-1β mRNA in a concentration-dependent manner.
Inhibited IL-1β induction with an IC50 of 21 nM.
Inhibited COX-2 induction with an IC50 of 42 nM.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 8-12 weeks old)[1]
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Dosage:10 mg/kg
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Administration:i.p.; 3 times (3-4, 6-8, and 19 hours after SE onset)
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Result:Regained weight faster than vehicle-treated SE mice, with significant difference in weight loss on day 2 post-SE (P = 0.0043).
Attenuated microgliosis (measured by IBA 1 positive area covered) in the amygdala (P = 0.0130), cortex (P = 0.0038), and hippocampus CA3 region (P = 0.0183) 4 days post-SE; showed a reducing trend in the hippocampus CA1 region.
Reduced SE-induced increases in hippocampal inflammatory mediator mRNA levels (P = 0.033).
Improved working memory, with an alternation index of 0.65 compared to 0.54 in vehicle-treated SE mice (P = 0.033); no impact on distance traveled in the Y-maze.
Restored recognition memory, with a discrimination index of 0.277 in the novel object recognition test (P < 0.0001), compared to 0.048 in vehicle-treated SE mice.
Chemical Information
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CAS No. 3120759-70-5
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Molecular Weight 346.43
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Formula C21H22N4O
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SMILES
O=C(C1=CC2=C(C(C)=NC=C2)N1C)NCCC3=C(C)NC4=CC=CC=C43
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Pyroptosis Solutions
Pyroptosis is a lytic inflammatory cell-death pathway executed by gasdermin pores, most classically through inflammasome-mediated activation of caspase-1, cleavage of gasdermin D, membrane pore formation, LDH release, and secretion of IL-1β and IL-18. The canonical pathway is commonly modeled by priming cells with an inflammatory signal such as LPS to induce pro-IL-1β and inflammasome components, followed by an activation signal such as ATP or nigericin to activate NLRP3, ASC speck formation, caspase-1 cleavage, GSDMD cleavage, cytokine release, and pyroptotic membrane rupture. The non-canonical pathway is triggered when cytosolic LPS activates mouse caspase-11 or human caspase-4/5, leading to GSDMD cleavage and pyroptosis, and this can secondarily activate NLRP3-dependent IL-1β release. Pyroptosis is linked to inflammatory injury, infection, cancer, liver disease, ocular disease, placental inflammation, and other disease phenotypes, but unresolved questions include which gasdermin fam
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)