Zetomipzomib maleate (KZR-616), a novel immunoproteasome inhibitor, effectively and selectively inhibits the LMP7 subunit (hLMP7/mLMP7 IC50: 39/57 nM) and LMP2 subunit (hLMP7/mLMP7 IC50: 131/179 nM) of the immunoproteasome. This compound shows promising potential for research in various autoimmune diseases.

Zetomipzomib maleate also inhibits MECL-1 subunit (IC 50 =623 nM) and constitutive proteasome β5 subunit (IC 50 =688 nM). Zetomipzomib maleate maintains LMP7 and LMP2 selective inhibition in MOLT-4 cells. Zetomipzomib maleate (250 nM) shows a comparable cytokine inhibition profile peripheral blood mononuclear cells (PBMC)[1]. Zetomipzomib maleate is an immunoproteasome-selective inhibitor identified based on the optimization of ONX-0914 (HY-13207) and PR-924 (HY-123587)[3].

Zetomipzomib maleate, administered intravenously (i.v.) at a dosage of 5 mg/kg, demonstrated effectiveness in the anticollagen antibody induced arthritis (CAIA) model[1]. This study utilized 7-8 week old female BALB/c mice, with dosing repeated on days 6, 8, 11, and 13. The results highlighted zetomipzomib maleate's potential in mitigating CAIA, marking it as efficacious in this specific animal model.