ONX 0914

Territorial Availability: Available through Bertin Technologies only in France

• Synonyms
  • N-?[2-?(4-?morpholinyl)?acetyl]?-?L-?alanyl-?O-?methyl-?N-?[(1S)?-?2-?[(2R)?-?2-?methyl-?2-?oxiranyl]?-?2-?oxo-?1-?(phenylmethyl)?ethyl]?-L-tyrosinamide
• Correlated keywords
  • 1161839-?04-?8 LMP7 immunoproteasome T cell inflammatory cytokine immunology ?1i inhibitor autoimmune disease ONX0914 inhibit biochemical ubiquitin-proteasome ?5i LMP7 ?-5i LMP-7 subunit mouse human block production IL-23 IL23 monocyte IFN-? IFN? IL-2 IL2 IL-17-producing IL17 TH17-polarizing condition in vitro TH-17 TH1 TH-1 differentiation vivo attenuate progression experimental model hematologic malignancies specialized inducible proteasome peptide histocompatibility complex MHC class I molecule cytotoxic replacement constitutive catalytic production restricted epitope
• Product Overview:
  The immunoproteasome is a specialized, inducible proteasome that generates peptides presented on major histocompatibility complex (MHC) class I molecules to cytotoxic T cells. Stimulation of cells with inflammatory cytokines such as IFN-? leads to the replacement of constitutive catalytic proteasome ? subunits with inducible ? subunits (?1i (LMP2), ?2i (MECL1), and ?5i (LMP7)), which are required for the production of certain MHC class I-restricted T cell epitopes. ONX 0914 is a selective inhibitor of the ?5i (LMP7) subunit of the immunoproteasome (IC50s = 65 and 73 nM for mouse and human, respectively) and demonstrates significantly weaker activity at the ?5 subunit of the constitutive proteasome (IC50s = 0.92 and 1.04 µM for mouse and human, respectively).{28373,28369} It can block the production of IL-23 by activated monocytes and the production of IFN-? and IL-2 by T cells.{28373} ONX 0914 can also inhibit IL-17-producing T cells under TH17-polarizing conditions in vitro and reduce TH1 and TH17 cell differentiation in vivo.{28372} This compound has been shown to attenuate disease progression in several experimental models of autoimmune disorders as well as in some hematologic malignancies.{28373,28370,28241,28371}