ONX-0914 (PR-957)

Catalog No.S7172 Batch:S717202

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Technical Data

Formula

C31H40N4O7
Molecular Weight 580.67 CAS No. 960374-59-8
Solubility (25°C)* In vitro DMSO 100 mg/mL (172.21 mM)
Ethanol 100 mg/mL (172.21 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO Corn oil
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description ONX-0914 (PR-957) is a potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome in a cell-free assay.
Targets
LMP7 [1]
(Cell-free assay)
~10 nM
In vitro 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%.[1]
In vivo In 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%.[1]
Features The first highly selective, small molecule inhibitor of the immunoproteasome. Potential use in cancer and autoimmune diseases (e.g. rheumatoid arthritis, inflammatory bowel disease, and lupus).

Protocol (from reference)

Animal Study:[1]
  • Animal Models

    collagen antibody–induced arthritis (CAIA) and collagen-induced arthritis (CIA)

  • Dosages

    2, 6 or 10 mg/kg

  • Administration

    i.v.

Customer Product Validation

Data from [Data independently produced by , , Cell Mol Bioeng, 2017, 10(2):174-185]

Data from [Data independently produced by , , Parasite Immunol, 2015, 37(11):599-604.]

Selleck's ONX-0914 (PR-957) has been cited by 18 publications

Immunoproteasome subunit β5i promotes perifascicular muscle atrophy in dermatomyositis by upregulating RIG-I [ RMD Open, 2023, 9(1)e002818] PubMed: 36854567
Interferon-α promotes neo-antigen formation and preferential HLA-B-restricted antigen presentation in pancreatic β-cells [ bioRxiv, 2023, 2023.09.15.557918] PubMed: 37745505
Interferon-α promotes neo-antigen formation and preferential HLA-B-restricted antigen presentation in pancreatic β-cells [ bioRxiv, 2023, 2023.09.15.557918] PubMed: 37745505
Corilagin induces human glioblastoma U251 cell apoptosis by impeding activity of (immuno)proteasome [ Oncol Rep, 2021, 45(4)34] PubMed: 33649855
Efficiency of the four proteasome subtypes to degrade ubiquitinated or oxidized proteins [ Sci Rep, 2020, 10(1):15765] PubMed: 32978409
Short-Term ONX-0914 Administration: Performance and Muscle Phenotype in Mdx Mice [ Int J Environ Res Public Health, 2020, 17(14):E5211] PubMed: 32707682
Expression of the immunoproteasome subunit β5i in non-small cell lung carcinomas [ J Clin Pathol, 2020, jclinpath-2020-206618] PubMed: 32943490
Integrative Multi-omics Analysis to Understand Cancer and Anticancer Therapy [ UNIVERSITY OF CALIFORNIA SAN DIEGO , 2020, ] PubMed: None
Genetic ablation and pharmacological inhibition of immunosubunit β5i attenuates cardiac remodeling in deoxycorticosterone-acetate (DOCA)-salt hypertensive mice [ J Mol Cell Cardiol, 2019, 137:34-45] PubMed: 31629736
Ablation and Inhibition of the Immunoproteasome Catalytic Subunit LMP7 Attenuate Experimental Abdominal Aortic Aneurysm Formation in Mice [ J Immunol, 2019, 202(4):1176-1185] PubMed: 30642978

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.