β5i-IN-2
β5i-IN-2 is a potent, selective, and orally active inhibitor of the immunoproteasome β5i subunit, with an IC50 of 0.08 μM against human β5i. β5i-IN-2 inhibits LPS (HY-D1056)- and IFN-γ-induced expression of IL-1β, IL-6, and TNF-α, and suppresses the JNK, ERK, and NF-κB signaling pathways. β5i-IN-2 can be used in research related to rheumatoid arthritis and ulcerative colitis.
For research use only. We do not sell to patients.
- CAS No.: 3119216-05-3
- Formula: C33H46N4O12
- Molecular Weight:690.74
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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]|
β5i 0.08 μM (IC50) |
In Vitro
β5i-IN-2 (compound ent-F10) (1 μM; serial dilutions; 10-15 min) potently and selectively inhibits the immunoproteasome β5i in cell-free lysate and purified proteasome assays, with an IC50 of 0.08 μM, and a selectivity index of 123.8 over the constitutive proteasome β5[1].
β5i-IN-2 exhibits low affinity for hERG ion channels in HEK293 cells, indicating a low risk of cardiotoxicity[1].
β5i-IN-2 (10-40 nM; pre-treatment for 1 h) reduces the mRNA expression of IL-1β, IL-6 and TNF-α in RAW 264.7 cells in a concentration-dependent manner after stimulation with LPS (100 ng/mL) and IFN-γ (20 ng/mL) for 24 h[1].
β5i-IN-2 (10-40 nM; 4 h pre-treatment) reduces JNK and ERK phosphorylation in RAW 264.7 cells in a concentration-dependent manner following 15 min of stimulation with LPS and IFN-γ, and restores IκBα protein levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW 264.7 murine macrophage cells
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Concentration:10, 20, 40 nM
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Incubation Time:1 h (pretreatment); 24 h (stimulation)
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Result:Concentration-dependently reduced IL-1β, IL-6 and TNF-α mRNA expression.
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Cell Line:RAW 264.7 murine macrophage cells
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Concentration:10, 20, 40 nM
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Incubation Time:4 h (pretreatment); 15 min (stimulation)
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Result:Reduced p-JNK and p-ERK levels and increased IκBα protein levels, with the strongest effects at 40 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:Sprague-Dawley (SD) rats (rheumatoid arthritis CIA model, arthritis index ≥2 at study start)[1]
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Dosage:2.5 mg/kg; 5.0 mg/kg; 10.0 mg/kg
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Administration:p.o.; once daily; 14 days
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Result:Dose-dependently reduced arthritis progression.
Day-14 arthritis index values were 7.13, 5.25, and 4.75 at 2.5, 5, and 10 mg/kg, respectively.
Produced paw-swelling inhibition rates of 17.2%, 32.3%, and 48.4%, respectively, on day 14, without significant body-weight loss.
Chemical Information
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CAS No. 3119216-05-3
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Molecular Weight 690.74
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Formula C33H46N4O12
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SMILES
O=C(N[C@@H](C)C(N[C@H](C(N[C@@H](C/C=C(C)/C)C([C@@]1(C)CO1)=O)=O)[C@H](O)C2=CC=C(OC)C=C2)=O)CN3CCOCC3.OC(/C=C\C(O)=O)=O
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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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
β5i-IN-2 Related Classifications
HY-187220 Related Classifications
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