ONX-0914 --- Immunoproteasome Inhibitor

Catalog No. size PriceQuantity
M60112-2S 2 mg solid $139
M60112-10S 10mg solid $556


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.

Product information

CAS Number: 960374-59-8

Molecular Weight: 580.67

Formula: C31H40N4O7

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

Smiles: C[C@H](NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1C=CC(=CC=1)OC)C(=O)N[C@@H](CC1C=CC=CC=1)C(=O)[C@]1(C)CO1


InChi: 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

Technical Data

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: ≥12 months 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

In Vitro:

ONX-0914 was used at 0.1-0.3 µM in vitro and in cellular assays.

In Vivo:

ONX-0914 was dosed to mice by either intravenous or subcutaneous administration at 2-10 mg/kg once a day for 5 days.


  1. Muchamuel T, et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. (2009) Nat Med. 15(7):781-7.
  2. Basler M, et al. Prevention of experimental colitis by a selective inhibitor of the immunoproteasome. (2010) J Immunol. 185(1):634-41.
  3. Huber EM, et al. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. (2012) Cell. 148(4):727-38.
  4. 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.

Products are for research use only. Not for human use.


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