Zetomipzomib (KZR-616) maleate, a first-in-class immunoproteasome inhibitor, selectively targets the LMP7 (IC50: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC50: 131/179 nM=hLMP2/mLMP2) subunits of the immunoproteasome. Zetomipzomib maleate has the potential for the research of multiple autoimmune diseases[2].In Vitro:Zetomipzomib maleate also inhibits MECL-1 subunit (IC50=623 nM) and constitutive proteasome β5 subunit (IC50=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).
Zetomipzomib maleate is an immunoproteasome-selective inhibitor identified based on the optimization of ONX-0914 (HY-13207) and PR-924 (HY-123587).In Vivo:Zetomipzomib maleate (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.