ONX 0914

  CAY-16271-1 1 mg

Data Sheet:     SDS:    

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960374-59-8  

A crystalline solid  

≥98%  

580,7  

-20  

-20  

1460  

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Description

 

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-γ leads to the replacement of constitutive catalytic proteasome β subunits with inducible β subunits (β1i (LMP2), β2i (MECL1), and β5i (LMP7)), which are required for the production of certain MHC class I-restricted T cell epitopes. ONX 0914 is a selective inhibitor of the β5i (LMP7) subunit of the immunoproteasome (IC50s = 65 and 73 nM for mouse and human, respectively) and demonstrates significantly weaker activity at the β5 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-γ 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}

 

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