ONX-0914

A potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome. It selectively inhibits low–molecular mass polypeptide-7 (LMP7, encoded by Psmb8), the chymotrypsin-like subunit of the immunoproteasome (IC₅₀ < 100 nM). ONX-0914 blocks presentation of LMP7-specific, MHC-I–restricted antigens in vitro and in vivo. Selective inhibition of LMP7 by ONX-0914 blocks production of interleukin-23 (IL-23) by activated monocytes and interferon-g and IL-2 by T cells.