受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C31H40N4O7 |
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分子量 | 580.67 | CAS No. | 960374-59-8 | ||||
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (172.21 mM) | ||||
Ethanol | 100 mg/mL (172.21 mM) | ||||||
Water | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <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. |
製品説明 | ONX-0914 (PR-957) is a potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome in a cell-free assay. |
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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] |
特徴 | 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). |
キナーゼアッセイ | Proteasome active site ELISA | |
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Briefly, samples (lysed cells or tissue homogenates) are treated for 1 hr at room temperature with the biotinylated active site probe PR-584 (5-15 μM). Samples are denatured by addition of SDS (0.9% final) and heating to 100°C for 5 minutes. The denatured samples are transferred to a 96-well or 384-well filter plate, mixed with streptavidin-sepharose beads (2.5-5 μL packed beads/well), and incubated for 1 hour at room temperature on a plate shaker. The beads are washed 5 times with 100-200 μL/well of ELISA buffer (PBS, 1% bovine serum albumin, 0.1% Tween-20) by vacuum filtration. The beads are incubated overnight at 4°C on a plate shaker with the following antibodies recognizing the six catalytic subunits diluted into ELISA buffer: β5, β1, and β2 diluted 1:3000; LMP7 and LMP2 diluted 1:5000; and MECL-1 diluted 1:1000. The beads are washed 5 times with 100-200 μL/well of ELISA buffer and incubated with HRP-conjugated secondary antibody (goat anti-rabbit for β5, rabbit anti-goat for MECL-1, and goat anti-mouse for LMP7, LMP2, β1 and β2) diluted 1:5000 in ELISA buffer and incubated 2 hours at room temperature on a plate shaker. The beads are washed 5 times with 100-200 μL/well of ELISA buffer and developed for chemiluminsecence signal using the supersignal ELISA pico substrate following the manufacturer's instructions. Luminescence is measured on a plate reader and converted to ng of proteasome or μg/mL of lysate by comparison with 20S proteasome or untreated cell lysate standard curves. | ||
動物実験 | 動物モデル | collagen antibody–induced arthritis (CAIA) and collagen-induced arthritis (CIA) |
投薬量 | 2, 6 or 10 mg/kg | |
投与方法 | i.v. |
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.]
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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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