ONX-0914

ONX 0914 (formerly PR-957) is an immunoproteasome inhibitor with potential treatment applications in autoimmune disorders, such as rheumatoid arthritis, inflammatory bowel disease and lupus. ONX-0914 (PR-957) has minimal cross-reactivity for the constitutive proteasome. The immunoproteasome regulates the production of several inflammatory cytokines, including Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), IL-17 and IL-23. ONX-0914 blocked progression of these diseases at well tolerated doses in preclinical models of rheumatoid arthritis and lupus. Treatment of LMP2(-/-)/MECL-1(-/-) double-deficient mice with ONX-0914 elicited a strong CTL response in lymphocytic choriomeningitis virus-infected mice.