EP4 receptor antagonist 8
EP4 receptor antagonist 8 is an orally active EP4 antagonist (human EP4 IC50 = 6.40 nM). EP4 receptor antagonist 8 significantly reduced paw and joint swelling, inflammatory cell infiltration, cartilage damage, pannus formation, and joint bone erosion in arthritis (AIA) mice in a dose-dependent manner. EP4 receptor antagonist 8 can be used for the study of inflammatory pain.
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- CAS. Nr.: 3068255-86-4
- Formel: C26H21ClN6O4
- Molecular Weight:516.94
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biologische Aktivität
Beschreibung
IC50 & Target
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EP4 6.4 nM (IC50) |
IL-6 |
In Vitro
EP4 receptor antagonist 8's (Compound 27i) (100 μg/mL, 0-60 min) metabolic stability in rat liver microsomes (RLM) decreases over time, with a remaining percentage of 41.44% at 60 minutes[1].
EP4 receptor antagonist 8 (24 h) exhibits a moderate plasma protein binding rate at 24 h (97.60 %)[1].
EP4 receptor antagonist 8 significantly reduces IL-6 levels in a dose-dependent manner in Lipopolysaccharides (HY-D1056) (LPS)-induced RAW 264.7 cells[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:Lipopolysaccharides (LPS)-induced RAW 264.7 cells
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Concentration:6.25 μM, 12.5 μM, 25 μM, 50 μM
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Incubation Time:Pretreated 1 h, then simulated with LPS for 24 h
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Result:Reduced LPS-induced IL-6 levels in a dose-dependent manner.
In Vivo
EP4 receptor antagonist 8 (5-20 mg/kg, p.o., once daily for 5 days) exhibits potent anti-inflammatory activity in a Kunming mouse acute inflammation model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Chronic arthritis was induced in the right hind paw using C57BL/6 mice (female, weighing 20-22 g) by injection of complete Freund's adjuvant (CFA)[1].
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Dosage:5 mg/kg, 10 mg/kg, 20 mg/kg
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Administration:I.p., once, performed 24 hours after CFA injection
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Result:Significantly improved the swelling of mice paws in a dose-dependent manner.
Increased the pain threshold; in both the hot plate test and the Von Frey test, the 20 mg/kg group showed the best effect within 120 minutes.
Reduced joint inflammation, cartilage damage, bone erosion, and pannus formation.
Reduced IL-1β, IL-6, and TNF-α positive cells in joint tissue.
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Animal Model:Acute ear inflammation and swelling were induced in male Kunming mice (weighing 20-22 g) by uniformly applying xylene (20 μL) to the right ear[1].
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Dosage:5 mg/kg, 10 mg/kg, 20 mg/kg
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Administration:P.o., once daily for 5 days
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Result:Showed excellent inhibitory effect, and the inhibitory rate was as high as 47.09 %, which was dose-dependent.
Chemical Information
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CAS. Nr. 3068255-86-4
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Molecular Weight 516.94
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Formel C26H21ClN6O4
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SMILES
O=C(O)C1=CC=C(CNC(C2=C3C=CC=CC3=NN2CCNC(NC4=CC=C(C#N)C=C4Cl)=O)=O)C=C1
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Protokoll
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Collagen-Induced Arthritis
Collagen-induced arthritis (CIA) is an autoimmune murine model of rheumatoid arthritis in which immunization with type II collagen (CII) emulsified in an adjuvant induces a T cell- and autoantibody-driven inflammatory arthritis characterized by synovial hyperplasia, immune cell infiltration, and joint destruction. The model typically relies on genetically susceptible mouse strains (e. g. , DBA/1) and reproduces key features of human rheumatoid arthritis, including anti-collagen immune responses and progressive joint inflammation. Disease onset generally occurs within ~3-4 weeks after immunization, depending on antigen/adjuvant combinations and protocol variation. The immunopathology is driven by adaptive immune activation against CII, leading to systemic and local joint inflammation mediated by pro-inflammatory cytokines and effector immune cells, making CIA a standard preclinical platform for evaluating immunomodulatory and anti-arthritic interventions.
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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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Formalin-Induced Paw Inflammation/Nociceptive Inflammation
The formalin-induced paw inflammation/nociceptive test is a chemical persistent pain model in rodents in which subcutaneous injection of formalin into the hind paw produces spontaneous nocifensive behaviors such as flinching and licking. The response is classically biphasic, consisting of an early acute phase (Phase I) reflecting direct activation of peripheral nociceptors (particularly C-fiber afferents), followed by a later prolonged phase (Phase II) associated with central sensitization in the spinal dorsal horn driven by sustained afferent input and inflammatory signaling. This model is widely used to evaluate analgesic and anti-inflammatory interventions because it captures both peripheral nociception and central sensitization processes within a single assay system.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)