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    ONX-0914 (PR-957)
    ONX-0914 (PR-957)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0690
    CAS #: 960374-59-8Purity ≥98%

    Description: ONX-0914 (also known as ONX0914; PR957) is a selective inhibitor of LMP7 and LMP2 subunits of immunoproteasomes with the potential to be used in autoimmune diseases including  rheumatoid arthritis, inflammatory bowel disease and lupus. It shows minimal cross-reactivity for the constitutive proteasome in a cell-free assay.  

    References: Nat Med. 2009 Jul;15(7):781-7.

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    Molecular Weight (MW)580.67
    CAS No.960374-59-8
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 100 mg/mL (172.2 mM) 
    Water: <1 mg/mL
    Ethanol: 100 mg/mL (172.2 mM) 
    Solubility (In vivo)2% DMSO+castor oil: 10 mg/mL

    Synonym: ONX0914; PR-957; ONX 0914; PR 957; ONX-0914; PR957; 

    Chemical Name: (S)-3-(4-methoxyphenyl)-N-((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanamide


    InChi Code: InChI=1S/C31H40N4O7/c1-21(32-27(36)19-35-13-15-41-16-14-35)29(38)34-26(18-23-9-11-24(40-3)12-10-23)30(39)33-25(28(37)31(2)20-42-31)17-22-7-5-4-6-8-22/h4-12,21,25-26H,13-20H2,1-3H3,(H,32,36)(H,33,39)(H,34,38)/t21-,25-,26-,31+/m0/s1

    SMILES Code: O=C(N[[email protected]@H](CC1=CC=CC=C1)C([[email protected]]2(C)OC2)=O)[[email protected]@H](NC([[email protected]@H](NC(CN3CCOCC3)=O)C)=O)CC4=CC=C(OC)C=C4

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    In Vitro

    In vitro activity: ONX-0914 is 20- to 40-fold more selective for LMP7 over the next most sensitive sites, β5 or LMP2. ONX-0914 blocks 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 blocks production of interleukin-23 (IL-23) by activated monocytes and interferon-gamma and IL-2 by T cells. LMP7 inhibition blocks production of IL-23 by ~90% and of tumor necrosis factor-α (TNF-α) and IL-6 by ~50%.

    Cell Assay: PBMCs were treated with 200 nM ONX-0914 for 1 hour and were exposure to 1 ng/ml LPS for 24 h. Supernatants were analyzed for expression of the inflammatory cytokines. ONX-0914 selectively inhibited LMP7 (> 80%). LMP7 inhibition blocked production of IL-23 by > 90% and of tumor necrosis factor-α (TNF-α) and IL-6 by ~ 50%. Higher concentrations of ONX-0914, which induce inhibition of LMP2 and MECL-1, further decreased secretion of TNF-α and IL-6, suggesting that these subunits have a role in cytokine regulation.

    In VivoIn mouse models of rheumatoid arthritis and lupus, ONX-0914 treatment reverses signs of disease and results in reductions in cellular infiltration, cytokine production and autoantibody levels at well-tolerated doses. The maximum tolerated dose (MTD) of ONX-0914 in mice to be 30 mg/kg body weight. IFN-g release is inhibited by ~60% at LMP7-selective concentrations of ONX-0914 and by ~90% at higher concentrations. Production of IL-2 is also inhibited by ~50%.
    Animal modelCollagen antibody–induced arthritis (CAIA) and collagen-induced arthritis (CIA)
    Formulation & DosageDissolved in 10% (w/v) sulfobutylether-β-cyclodextrin and 10 mM sodium citrate (pH 6); 2, 6 or 10 mg/kg; i.v. injection

    Nat Med. 2009 Jul;15(7):781-7.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    ONX-0914 (PR-957)


    ONX-0914 (PR-957)


    ONX-0914 (PR-957)


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