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^[1].

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 (K_I = 1.1 × 10⁰ μM for LMP7, K_I = 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.

Immunoproteasome-IN-2 (compound A33) (5 mg/ kg, i.v., three times weekly for 2 weeks) exhibits potent anti-inflammatory efficacy in anticollagen antibody-induced arthritis (CAIA) induced in BALB/c mice^[1].
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.

612.71

C₃₂H₄₄N₄O₈

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

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Wu J, et al. Discovery of Novel Potent and Safe Immunoproteasome Inhibitors with Bridged Ring for Anti-Inflammatory Therapy. J Med Chem. 2025 Nov 27;68(22):24579-24602.  [Content Brief]