产品说明书

ONX-0914

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Chemical Structure| 960374-59-8 同义名 : PR-957
CAS号 : 960374-59-8
货号 : A354826
分子式 : C31H40N4O7
纯度 : 99%+
分子量 : 580.672
MDL号 : MFCD26794217
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(60.28 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+castor oil 10 mg/mL

生物活性
描述 The immunoproteasome is a class of proteasome predominantly synthesized in monocytes and lymphocytes. ONX-0914 is a selective inhibitor of low-molecular mass polypeptide-7 (LMP7), the chymotrypsin-like subunit of the immunoproteasome. In human peripheral blood mononuclear cells (PBMCs), 100 nM ONX-0914 blocked the activity of LMP7 by 480% with minimal inhibitory effect on LMP2 or MECL-1. ONX-0914 at 200 nM also inhibited the production of inflammatory cytokines, such as IL-23, TNF-α and IL-6, in LPS-stimulated human PBMCs. ONX-0914 at the doses of 25-300 nM inhibited chymotrypsin-like activity of liver proteasomes isolated from WT mice but not Psmb8-/- mice. In BALB/c mice, an intravenous administration of ONX-0914 at 1-10 mg/kg inhibited the activity of LMP7 in both blood and kidney. The intravenous treatment of female C57BL/6 mice with ONX-0914 (6 mg/kg) for 5 days suppressed the infection induced by recombinant vaccinia virus expressing UTY protein. In a mouse model of collagen antibody-induced arthritis, ONX-0914 at 2, 6, or 10 mg/kg delayed disease progression in a concentration-dependent manner and completely ameliorated visible clinical signs at the dose of 10 mg/kg[2].
作用机制 ONX-0914 is a selective inhibitor for the chymotrypsin-like subunit of immunoproteasome, LMP7. It contains a ketoepoxide pharmacophore that covalently modifies the proteasomal active sites of LMP7.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human Raji cells Function assay Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry, IC50=5.7 nM 25006746
human Raji cells Function assay Inhibition of 20s proteasome subunit beta-5c in human Raji cells using BODIPY-NC005 by fluorescent densitometry, IC50=0.054 μM 25006746
human Raji cells Function assay Inhibition of proteasome subunit beta-1i in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry, IC50=0.46 μM 25006746
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.72mL

0.34mL

0.17mL

8.61mL

1.72mL

0.86mL

17.22mL

3.44mL

1.72mL
参考文献

[1]Muchamuel T, Basler M, Aujay MA, Suzuki E, Kalim KW, Lauer C, Sylvain C, Ring ER, Shields J, Jiang J, Shwonek P, Parlati F, Demo SD, Bennett MK, Kirk CJ, Groettrup M. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med. 2009 Jul;15(7):781-7. doi: 10.1038/nm.1978. Epub 2009 Jun 14. Erratum in: Nat Med. 2009 Nov;15(11):1333. PMID: 19525961.