ONX-0914 (PR-957)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
ONX-0914 (PR-957)是一种有效的免疫蛋白酶体（immunoproteasome）抑制剂。免疫蛋白酶体是蛋白酶体的一种形式，产生的多肽由主要组织相容性复合体（MHC）I类分子呈递给细胞毒性T细胞。在人和小鼠细胞中，ONX-0914选择性地诱导免疫蛋白酶体亚基β5i（低分子量多肽7/LMP7），而非组成型蛋白酶体亚基β5的S1结合口袋的构象变化。ONX-0914能够阻断人外周血单核细胞（PBMCs）产生促炎细胞因子，激活小鼠脾细胞，抑制在Th17极化细胞因子存在下产生IL-17的T细胞，在小鼠模型中抑制糖尿病、关节炎和结肠炎等疾病的发展。
参考文献：
Denise Niewerth, Niels E. Franke, Gerrit Jansen, Yehuda G. Assaraf, Johan van Meerloo, Christopher. Kirk, Jeremiah Degenhardt, Janet Anderl, Aaron D. Schimmer, Sonja Zweegman, Valerie de Haas, Terzah M. Horton, Gertjan J.L. Kaspers, and Jacqueline Cloos. Higer ratio immune vs. constitutive proteasome level as novel indicator of sensitivity of pediatric acute leukemia cells to proteasome inhibitors. Haematologica 2013.
Khalid W. Kalim, Michael Basler, Christopher J. Kirk and Marcus Groettrup. Immunoproteasome subunit LMP7 deficiency and inhibition suppresses Th1 and Th17 but enhances regulatory T cell differentiation. J Immunol 2012; 189:4182-4193
- 1. Kris Genelyn Dimasuay, Niccolette Schaunaman, et al. "Airway epithelial immunoproteasome subunit LMP7 protects against rhinovirus infection." Sci Rep. 2022 Aug 25;12(1):14507. PMID: 36008456
- 2. Kirby L, Jin J, et al. “Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination." Nat Commun. 2019 Aug 29;10(1):3887. PMID: 31467299
- 3. Jimenez-Guardeño JM, Apolonia L, et al. "Immunoproteasome activation enables human TRIM5α restriction of HIV-1." Nat Microbiol. 2019 Jun;4(6):933-940. PMID: 30886358
- 4. Leslie Kirby, Jing Jin, et al. "Oligodendrocyte Precursor Cells Are Co-Opted by the Immune System to Cross-Present Antigen and Mediate Cytotoxicity." bioRxiv. 2018 November 4.
- 5. Dimasuay KG, Sanchez A, et al."Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways." Clin Sci (Lond). 2018 Aug 16;132(15):1711-1723. PMID: 29980604
- 6. Liu RT, Zhang P, et al. "ONX-0914, a selective inhibitor of immunoproteasome, ameliorates experimental autoimmune myasthenia gravis by modulating humoral response." J Neuroimmunol. 2017 Oct 15;311:71-78. PMID: 28844501
- 7. Ortega-Atienza S, Krawic C, et al. "20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death." Sci Rep. 2017 Apr 5;7(1):654. PMID: 28381880
- 8. Chen, S., et al. "Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages." Cell Death & Differentiation (2016). PMID: 26990663
| Storage | Store at -20°C |
| M.Wt | 580.67 |
| Cas No. | 960374-59-8 |
| Formula | C31H40N4O7 |
| Synonyms | ONX-0914,PR-957 |
| Solubility | ≥29.03 mg/mL in DMSO; insoluble in H2O; ≥69 mg/mL in EtOH |
| Chemical Name | (2S)-3-(4-methoxyphenyl)-N-[(2S)-1-(2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide |
| SDF | Download SDF |
| Canonical SMILES | CC(C(=O)NC(CC1=CC=C(C=C1)OC)C(=O)NC(CC2=CC=CC=C2)C(=O)C3(CO3)C)NC(=O)CN4CCOCC4 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验[1]： | |
|
细胞系 |
人外周血单核细胞（PBMC） |
|
溶解方法 |
在DMSO中的溶解度>10 mM。为了获得更高的浓度，可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
|
反应条件 |
200 nM；1 h |
|
应用 |
将PBMC用200 nM的ONX-0914处理1小时后，于1 ng/ml的LPS中暴露24小时，上清用于分析炎性细胞因子的表达。ONX-0914选择性地抑制LMP7（> 80%）。LMP7的抑制阻断了大于90%的IL-23的产生和约50%的肿瘤坏死因子α（TNF-α）和IL-6的产生。诱导LMP2和MECL-1抑制的更高浓度的ONX-0914可进一步减少TNF-α和IL-6的分泌，表明这些亚基在细胞因子的产生中起重要作用。 |
| 动物实验[1]： | |
|
动物模型 |
胶原抗体诱导的关节炎（CAIA）BALB/c小鼠模型；胶原诱导的关节炎（CIA）DBA1/J小鼠模型 |
|
剂量 |
2、6和10 mg/kg；静脉注射 |
|
应用 |
ONX-0914以剂量依赖的方式阻断疾病的发展，在最高剂量下完全改善疾病的明显迹象。PR-957以2 mg/kg的剂量给药的治疗反应表明，LMP7的单独抑制即可阻止疾病的发展。在T细胞和B细胞依赖的CIA模型中，ONX-0914也诱导快速的治疗反应。免疫蛋白酶体的抑制与循环中自身抗体及胶原寡聚基质蛋白（COMP）水平的下降相关，COMP是软骨破坏的标志物。 |
|
注意事项 |
请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。 |
|
References: [1] Muchamuel T, Basler M, Aujay M A, et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nature medicine, 2009, 15(7): 781-787. |
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| 描述 | ONX-0914 (PR-957)是一种有效的和选择性的免疫蛋白酶体（immunoproteasome）抑制剂，对组成型蛋白酶体具有最低的交叉反应性。 | |||||
| 靶点 | LMP7 | |||||
| IC50 | ~10 nM | |||||
质量控制和MSDS
- 批次:
化学结构
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