R-130823
R-130823 is an orally active, highly selective p38α inhibitor with an IC50 of 22 nM against p38α, an IC50 of 820 nM against p38β, and no activity against p38γ or p38δ. R-130823 downregulates downstream cartilage degradation and inflammatory mediators, and inhibits the release of MMP-13, MMP-1 and PGE2. R-130823 reduces hind paw swelling, improves hyperalgesia, and blocks arthritis progression. R-130823 is applicable to research related to osteoarthritis and rheumatoid arthritis.
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- CAS No.: 321344-32-5
- Formule: C28H26FN3
- Masse moléculaire:423.52
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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p38α 22 nM (IC50) |
p38β 820 nM (IC50) |
MMP13 |
MMP-1 |
R-130823 potently inhibits purified p38α kinase (IC50 = 22 nM), moderately inhibits purified p38β kinase (IC50 = 820 nM), and shows no activity against p38γ or p38δ[1].
R-130823 (4-2500 nM; 1 h) inhibits the release of MMP-13 (IC50 = 20 nM), MMP-1 (IC50 = 230 nM) and PGE2 (IC50 = 3.9 nM) induced by IL-1β in human primary chondrocytes[1].
R-130823 (0.1-10 μM; incubated for 3 weeks with weekly compound supplementation) inhibits IL-1α/oncostatin M-induced collagen cleavage in bovine nasal cartilage explants, with an IC50 of 510 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
R-130823 (1-30 mg/kg; p.o.; single dose) dose-dependently ameliorates adjuvant-induced hyperalgesia in rats, with sustained analgesic activity lasting up to 24 hours at the highest tested dose of 30 mg/kg[2].
R-130823 (3-30 mg/kg/day; p.o.; once daily; 14 days) dose-dependently blocks arthritis progression in murine collagen-induced arthritis, with statistically significant suppression of arthritis index (P < 0.0001) and reduced joint tissue inflammation at the highest tested dose of 30 mg/kg/day[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Lewis rats (female, 7 weeks old, adjuvant-induced arthritis model)[2]
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Dosage:1 mg/kg/day; 3 mg/kg/day; 10 mg/kg/day; 30 mg/kg/day
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Administration:p.o.; twice daily; 7 days
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Result:Reduced hind paw swelling volume by 18% at 1 mg/kg/day on Day 25.
Reduced hind paw swelling volume by 31% at 3 mg/kg/day on Day 25.
Reduced hind paw swelling volume by 45% at 10 mg/kg/day on Day 25.
Reduced hind paw swelling volume by 55% at 30 mg/kg/day on Day 25.
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Animal Model:Lewis rats (male, 5 weeks old, adjuvant-induced hyperalgesia model)[2]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; single dose
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Result:Produced dose-dependent reductions in pain score, with effects observed within 1 hour, maximum effect at 2 hours post-administration, and sustained analgesic activity up to 24 hours post-administration.
Decreased pain score by 74% at 30 mg/kg at 24 hours post-administration, with statistical significance relative to controls between 1 and 24 hours.
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Animal Model:DBA1/J mice (male, 5 weeks old, collagen-induced arthritis model)[2]
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Dosage:3 mg/kg/day; 10 mg/kg/day; 30 mg/kg/day
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Administration:p.o.; once daily; 14 days
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Result:Dose-dependently suppressed arthritis progression.
Showed no increase in arthritis index over the treatment period at 30 mg/kg/day, with a statistically significant lower index relative to vehicle controls (P < 0.0001).
Reduced severity of synovial neutrophil infiltration, fibrin deposition, synoviocyte proliferation, fibroblast proliferation, joint cavity debris, and cartilage cell desquamation in knee joints at 30 mg/kg/day relative to vehicle controls.
Chemical Information
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CAS No. 321344-32-5
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Masse moléculaire 423.52
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Formule C28H26FN3
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SMILES
FC1=CC=C(C=C1)C2=C(C(C3=CCN(CC3)CCC4=CC=CC=C4)=CN2)C5=CC=NC=C5
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Wada Y, et al. Novel p38 mitogen-activated protein kinase inhibitor R-130823 protects cartilage by down-regulating matrix metalloproteinase-1,-13 and prostaglandin E2 production in human chondrocytes. Int Immunopharmacol. 2006;6(2):144-155. [Content Brief]
[2]. Wada Y, et al. R-130823, a novel inhibitor of p38 MAPK, ameliorates hyperalgesia and swelling in arthritis models. Eur J Pharmacol. 2005;506(3):285-295. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
R-130823 Related Classifications
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