ONX-0914 (PR-957)
(Synonyms: ONX-0914,PR-957) 目录号 : GC15778
A selective inhibitor of the β5i (LMP7) subunit of the immunoproteasome
Cas No.:960374-59-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment: [1] | |
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Cell lines |
Human peripheral blood mononuclear (PBMC)cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
200 nM, 1 hour |
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Applications |
PBMCs were treated with 200 nM ONX-0914 for 1 hour and were exposure to 1 ng/ml LPS for 24 h. Supernatants were analyzed for expression of the inflammatory cytokines. ONX-0914 selectively inhibited LMP7 (> 80%). LMP7 inhibition blocked production of IL-23 by > 90% and of tumor necrosis factor-α (TNF-α) and IL-6 by ~ 50%. Higher concentrations of ONX-0914, which induce inhibition of LMP2 and MECL-1, further decreased secretion of TNF-α and IL-6, suggesting that these subunits have a role in cytokine regulation. |
| Animal experiment: [1] | |
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Animal models |
Collagen antibody–induced arthritis (CAIA) model in BALB/c mice Collagen-induced arthritis (CIA) model in DBA1/J mice |
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Dosage form |
Intravenous injection, 2, 6 and 10 mg per kg body weight |
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Applications |
ONX-0914 blocked disease progression in a dose-dependent manner and completely ameliorated visible signs of disease at the highest dose. Inhibition of LMP7 alone was sufficient to block disease progression, as evidenced by the therapeutic response to PR-957 administered at 2 mg per kg body weight. ONX-0914 treatment also induced a rapid therapeutic response in the T and B cell–dependent CIA model. Immunoproteasome inhibition was associated with a decrease in circulating levels of autoantibodies and collagen oligomeric matrix protein (COMP), a marker for cartilage breakdown. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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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ONX-0914, previously known as PR-975, is a potent inhibitor of immunoproteasome, a form of proteasome generating peptides presented on major histocompatibility complex (MHC) class I molecule to cytotixic T cells, which selectively induces conformational changes in the S1 binding pocket of the immunoproteasome subunit β5i (low molecular mass polypeptide 7/LMP7) rather than the constitutive proteasome subunit β5 in human and mouse cells. ONX-0914 is able to block the production of proinflammatory cytokines from human peripheral blood mononuclear cells (PBMCs), activate mouse splenocytes, inhibit IL-17-producing T cells under TH17-polarizing cytokines in vitro, and attenuate disease progression of diabetes, arthritis, and colitis in mouse models.
Reference
[1].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.
[2].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
| Cas No. | 960374-59-8 | SDF | |
| 别名 | ONX-0914,PR-957 | ||
| 化学名 | (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 | ||
| 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 | ||
| 分子式 | C31H40N4O7 | 分子量 | 580.67 |
| 溶解度 | ≥ 29.0335mg/mL in DMSO, ≥ 69 mg/mL in EtOH | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7221 mL | 8.6107 mL | 17.2215 mL |
| 5 mM | 0.3444 mL | 1.7221 mL | 3.4443 mL |
| 10 mM | 0.1722 mL | 0.8611 mL | 1.7221 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。