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.
For research use only. We do not sell to patients.
- CAS No.: 321344-32-5
- Formula: C28H26FN3
- Molecular Weight:423.52
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
p38α 22 nM (IC50) |
p38β 820 nM (IC50) |
MMP13 |
MMP-1 |
In Vitro
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. Further protocols information, click here.
In Vivo
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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Molecular Weight 423.52
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Formula 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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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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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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Mitochondrial membrane-potential fluorescent assay
Mitochondrial membrane potential fluorescent assays estimate ΔΨm in living cells using lipophilic cationic dyes such as TMRM, TMRE, rhodamine 123, and JC-1, which accumulate in mitochondria according to membrane polarization; loss of signal after FCCP or CCCP treatment is interpreted as mitochondrial depolarization. TMRM/TMRE and rhodamine 123 are commonly used for semi-quantitative live-cell microscopy or flow cytometry, while JC-1 can report a shift from red aggregate fluorescence to green monomer fluorescence during depolarization; interpretation requires controls because dye concentration, quenching mode, cell type, dye efflux, and mitochondrial mass can affect fluorescence independently of ΔΨm.
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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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Mitochondrial membrane-potential and mitochondrial mass staining
Mitochondrial membrane potential staining measures the electrochemical polarization across the mitochondrial inner membrane in live cells using lipophilic cationic fluorescent probes; early rhodamine-based work showed that selective mitochondrial dye accumulation is lost when the mitochondrial transmembrane potential is dissipated. JC-1 reports mitochondrial polarization by shifting from green monomer fluorescence to red J-aggregate fluorescence as dye concentration increases within energized mitochondria; therefore, the red/green fluorescence ratio is used as a relative readout of mitochondrial membrane potential. TMRE or TMRM staining provides a single-channel relative readout because these cationic rhodamine esters accumulate in polarized mitochondria, and lower fluorescence indicates reduced mitochondrial polarization when acquisition and dye-loading conditions are controlled. Mitochondrial mass staining is commonly performed with MitoTracker Green FM or related MitoTracker dyes as
Purity & Documentation
References
[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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