ONX-0914 is an immunoproteasome inhibitor. It selectively inhibits low–molecular 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.
CAS Number: 960374-59-8
Molecular Weight: 580.67
Chemical Name: (S)-3-(4-methoxyphenyl)-N-((S)-1-((S)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanamide
Appearance: Solid Power.
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: DMSO up to 100 mM
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥360 days if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
ONX-0914 was used at 0.1-0.3 µM in vitro and in cellular assays.
ONX-0914 was dosed to mice by either intravenous or subcutaneous administration at 2-10 mg/kg once a day for 5 days.
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- Basler M, et al. Prevention of experimental colitis by a selective inhibitor of the immunoproteasome. (2010) J Immunol. 185(1):634-41.
- Huber EM, et al. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. (2012) Cell. 148(4):727-38.
- Kalim KW, et al. Immunoproteasome subunit LMP7 deficiency and inhibition suppresses Th1 and Th17 but enhances regulatory T cell differentiation. (2012) J Immunol. 189(8):4182-93.
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