ONX-0914 (PR-957)

製品コードS7172 バッチS717202

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₃₁H₄₀N₄O₇

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）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (8.61mM)	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.

溶剤液（一定の濃度）を調合する

生物活性

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.
in vitro	ONX-0914 (PR-957) is 20- to 40-fold more selective for LMP7 over the next most sensitive sites, β5 or LMP2. It 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 this compound 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, treatment with ONX-0914 (PR-957) 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 this compound in mice is 30 mg/kg body weight. IFN-g release is inhibited by ~60% at LMP7-selective concentrations 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).

プロトコル(参考用のみ)

キナーゼアッセイ	Proteasome active site ELISA
キナーゼアッセイ	Briefly, samples (lysed cells or tissue homogenates) are treated for 1 hr at room temperature with the biotinylated active site probe ONX-0914 (PR-957) (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.

参考

https://pubmed.ncbi.nlm.nih.gov/19525961/

カスタマーフィードバック

: 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の高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells [ Nat Commun, 2025, 16(1):765]	PubMed: 39824805
Targeting Immunoproteasome in Polarized Macrophages Ameliorates Experimental Emphysema Via Activating NRF1/2-P62 Axis and Suppressing IRF4 Transcription [ Adv Sci (Weinh), 2024, 11(44):e2405318]	PubMed: 39356034
20S constitutive proteasome, 20S immunoproteasome, and cathepsin S are high-sensitivity and independent markers of immunological activity in relapsing-remitting type of multiple sclerosis [ J Neurochem, 2024, 10.1111/jnc.16165]	PubMed: 38923513
Impaired immunoproteasomal function exacerbates renal ischemia-reperfusion injury [ Exp Mol Pathol, 2024, 140:104939]	PubMed: 39426027
Immunoproteasome subunit β5i promotes perifascicular muscle atrophy in dermatomyositis by upregulating RIG-I [ RMD Open, 2023, 9(1)e002818]	PubMed: 36854567
Evaluation of Proteasome and Immunoproteasome Levels in Plasma and Peritoneal Fluid in Patients with Endometriosis [ Int J Mol Sci, 2023, 24(18)14363]	PubMed: 37762666
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

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。