Immunoproteasome-IN-2
Immunoproteasome-IN-2 is selective immunoproteasome inhibitor with IC50 = 232.3 nM for LMP7, IC50 = 9384.9 nM for β5. Immunoproteasome-IN-2 exhibits ancillary inhibitory activity against LMP2 and MECL-1 subunits. Immunoproteasome-IN-2 demonstrates anti-inflammatory efficacy in a mouse model of arthritis and shows a favorable safety profile in toxicological studies with reduced hepatotoxicity and hematotoxicity. Immunoproteasome-IN-2 has LMP7/β5 selectivity directly correlated with lower systemic toxicity. Immunoproteasome-IN-2 can be employed for research in arthritis.
For research use only. We do not sell to patients.
- Formula: C32H44N4O8
- Molecular Weight:612.71
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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
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Immunoproteasome-IN-2 (compound A33) (1.37-3000 nM) has inhibitory activity across each immunoproteasome subunit with IC50 = 12.5 nM for LMP7, IC50 = 2022.3 nM for β5, IC50 = 1043.7 nM for LMP2 and IC50 = 570.2 nM for MECL-1 in Molt-4 cell (human leukemia T-cell)[1].
Immunoproteasome-IN-2 (1.37-3000 nM) exhibits excellent binding efficiency with LMP7 and forms a covalent bond more rapidly with LMP7 than with β5 in mouse B lymphoma cells (KI = 1.1 × 100 μM for LMP7, KI = 2.07 × 101 μM for β5.)[1].
Immunoproteasome-IN-2 has no low risk of cardiac toxicity with IC50 >30 μM for hERG, outstanding selectivity toward immunoproteasome subunit with no inhibitory potency against β1 (IC50 > 30 μM) subunits in HEK293 HERG cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | C0 | T1/2 | AUC0-t | AUC0-inf | CL | Vdss |
|---|---|---|---|---|---|---|---|---|
| Mice | 5 mg/kg | i.v. | 88000 ng/mL | 12.2 min | 929 ng·h/mL | 932 ng·h/mL | 90.1 mL/min/kg | 0.88 L/kg |
Immunoproteasome-IN-2 (20 mg/kg, i.v.) do not cause any SD rat death in the acute toxicity assay and maintained the levels of lymphocyte, platelet, and reticulocyte within the normal fluctuation range in hematological analysis[1].
Immunoproteasome-IN-2 (5 mg/kg, i.v.) has inhibitory activity against LMP7 (1.5% of relative activity), moderate inhibitory effect on LMP2 and MECL-1 (44.5 and 49.2% of relative activity, respectively) in the spleen and low inhibitory efficacy against β5 subunit in the kidney (76.9% of relative activity) in BALB/c mouse spleen[1].
Immunoproteasome-IN-2 (5-20 mg/kg, i.v., twice weekly for four consecutive weeks) exhibits a favorable safety profile in SD Rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:anticollagen antibody-induced arthritis (CAIA) induced in BALB/c mice[1]
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Dosage:5 mg/kg
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Administration:i.v., three times weekly for 2 weeks
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Result:Reduce the thickness of the paws, and the final CAIA score was less than 5.
Did not cause death or significant weight loss.
Exerted its efficacy by inhibiting the LMP2 and MECL-1 subunits, but not LMP7.
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Animal Model:SD Rats[1]
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Dosage:5 mg/kg, 10 mg/kg, and 20 mg/kg
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Administration:i.v., twice weekly for four consecutive weeks
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Result:Observed no mortality at any dosage.
Did not induce any significant adverse effects on hematological parameters or liver function across all tested doses.
Chemical Information
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Molecular Weight 612.71
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Formula C32H44N4O8
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SMILES
O=C(N[C@H](C(N[C@H](C(N[C@H](C([C@@]1(OC1)C)=O)CC2=CCCCC2)=O)[C@@H](C3=CC=C(N=C3)OC)O)=O)CO)C45CC(CC5)CC4
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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)
Immunoproteasome-IN-2 Related Classifications
HY-179394 Related Classifications
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