| 产品介绍 |
ONX-0914 is an immunoproteasome inhibitor. It selectively inhibits low鈥搈olecular mass polypeptide-7 (LMP7, encoded by Psmb8), the chymotrypsin-like subunit of the immunoproteasome, with an IC50 < 100 nM. It blocked presentation of LMP7-specific, MHC-I–restricted antigens in vitro and in vivo with minimal cross-reactivity for the constitutive proteasome. Selective inhibition of LMP7 by ONX-0914 blocked production of interleukin-23 (IL-23) by activated monocytes and interferon-gamma and IL-2 by T cells. In mouse models of rheumatoid arthritis and lupus, ONX-0914 treatment reversed signs of disease and resulted in reductions in cellular infiltration, cytokine production and autoantibody levels at well-tolerated doses. ONX 0914 is a good chemical probe to reveal a unique role for LMP7 in controlling pathogenic immune responses and provide a therapeutic rationale for autoimmune disorders, such as rheumatoid arthritis, inflammatory bowel disease and lupus.
|
