Zetomipzomib (KZR-616), a first-in-class inhibitor of the immunoproteasome, selectively targets the LMP7 (IC₅₀: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC₅₀: 131/179 nM=hLMP7/mLMP7) subunits of the immunoproteasome. Zetomipzomib has the potential for the research of multiple autoimmune diseases^[1][2].

Zetomipzomib also inhibits MECL-1 subunit (IC₅₀=623 nM) and constitutive proteasome β5 subunit (IC₅₀=688 nM). Zetomipzomib maintains LMP7 and LMP2 selective inhibition in MOLT-4 cells. Zetomipzomib (250 nM) shows a comparable cytokine inhibition profile peripheral blood mononuclear cells (PBMC)^[1]. Zetomipzomib is an immunoproteasome-selective inhibitor identified based on the optimization of ONX-0914 (HY-13207) and PR-924 (HY-123587)^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Zetomipzomib (5 mg/kg; i.v.; dosing was repeated on days 6, 8, 11, and 13) shows efficacy in the anticollagen antibody induced arthritis (CAIA) model^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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1629677-75-3

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• [1]. Johnson HWB, et al. Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)  [Content Brief]

  [2]. Muchamuel T, et al. FRI0296 Kzr-616, a selective inhibitor of the immunoproteasome, blocks the disease progression in multiple models of systemic lupus erythematosus (SLE). Annals of the Rheumatic Diseases 2018;77:685.

  [3]. Xi J, et al. Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases. Eur J Med Chem. 2019;182:111646.  [Content Brief]