| ONX-0914, also known as PR-957, is a potent inhibitor of the immunoproteasome with minimal cross-reactivity for the constitutive proteasome. ONX-0914 selectively inhibits low-molecular mass polypeptide-7 (LMP7), the subunit specific for the immunoproteasome that catalyzes the chymotyrpsion-like activity, with an IC50 < 100 nM. Cell culture and animal studies have shown that ONX-0914 blocks the production of proinflammatory cytokines including interleukin-6 and 17, indicating that it has potential uses in the treatment of some autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease and lupus. Dose: 0.1-0.5 µM for in vitro or cell couture assays, intravenous or subcutaneous administration at 2-10 mg/Kg daily for 5-7 days for animal studies. |
