ONX 0914

Synthetic. Chemical. CAS: 960374-59-8. Formula: C31H40N4O7. MW: 580.7. Synthetic. Potent and selective 20S immunoproteasome inhibitor. Targets the beta5i subunit [LMP7] of the 20S immunoproteasome (IC50=73nM) and with minimal crossreactivity to the chymotrypsin-like beta5 subunit of the constitutive 20S proteasome (IC50=1.04µM). Potent anti-inflammatory and anticancer agent. Inhibits production of pro-inflammatory cytokines and can induce apoptosis in vitro. Inhibits presentation of LMP7-specific, MHC-I-restricted antigens in vitro and in vivo, which consequently blocks production of interleukin-23 (IL-23) by activated monocytes and IFN-gamma and IL-2 by T cells. Can also inhibit IL-17-producing T cells under TH17-polarizing conditions in vitro and reduce TH1 and TH17 cell differentiation in vivo. Shown to attenuate disease progression in several experimental models of autoimmune disorders, such as rheumatoid arthritis, inflammatory bowel disease and lupus, as well as in some hematologic malignancies and other cancer types.