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Oprozomib (ONX-0912)

现货
Catalog No.
A1934
蛋白酶体抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,410.00
现货
5mg
¥ 1,050.00
现货
10mg
¥ 1,600.00
现货
25mg
¥ 3,000.00
现货
100mg
¥ 6,000.00
现货

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Background

ONX-0912 (as known as oprozomib), discovered during a medicinal chemistry effort using tripeptide epoxyketones, is an orally bio-available and potent proteasome inhibitor that inhibits growth and induces apoptosis in bortezomib resistant multiple myeloma (MM) cells. Although ONX-0912, an analog of carfilzomib, is structurally distinct from bortezomib, it possesses the same ability as bortezomib to predominantly inhibit chymotrypsin-like activity of the proteasome. ONX-0912 exhibits significant anti-MM activities to reduce tumor progression and prolong survival in many animal tumor model studies, which are associated with activation of caspase-3, caspase-8, caspase-9, and poly(ADP) ribose polymerase and inhibition of anglogensis and MM cells migration.

Reference

Dharminder Chauhan, Ajita V. Singh, Monette Aujay, Christopher J. Kirk, Madhavi Bandi, Bryan Ciccarelli, Noopur Raje, Paul Richardson, and Kenneth C. Anderson. A novel oraaly active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood 2010; 116(23): 4906-4915

文献引用

1.Felix Lambrecht. "Computational methods for the structure determination of highly dynamic molecular machines by cryo-EM." Georg-August-Universität Göttingen. 2019.
2.McCourt JL, Talsness DM, et al. "Mouse models of two missense mutations in actin-binding domain 1 of dystrophin associated with Duchenne or Becker muscular dystrophy." Hum Mol Genet. 2018 Feb 1;27(3):451-462. PMID:29194514
3.Haselbach D, Schrader J, et al. "Long-range allosteric regulation of the human 26S proteasome by 20S proteasome-targeting cancer drugs." Nat Commun. 2017 May 25;8:15578. PMID:28541292
4.Schrader J, Henneberg F, et al. "The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design." Science. 2016 Aug 5;353(6299):594-8. PMID:27493187
5.Vandewynckel YP, Coucke C, et al. "Next-generation proteasome inhibitor oprozomib synergizes with modulators of the unfolded protein response to suppress hepatocellular carcinoma."Oncotarget. 2016 Jun 7;7(23):34988-5000. PMID:27167000

Chemical Properties

Physical AppearanceA solid
StorageDesiccate at -20°C
M.Wt532.61
Cas No.935888-69-0
FormulaC25H32N4O7S
SynonymsONX-0912,ONX0912,ONX 0912,PR 047,Oprozomib
Solubility≥26.6mg/mL in DMSO
Chemical NameN-[(2S)-3-methoxy-1-[[(2S)-3-methoxy-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide
SDFDownload SDF
Canonical SMILESCC1=NC=C(S1)C(=O)NC(COC)C(=O)NC(COC)C(=O)NC(CC2=CC=CC=C2)C(=O)C3(CO3)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

细胞实验:

细胞系

人头颈部鳞状细胞癌(HNSCC)细胞系UMSCC-22A、UMSCC-22B、1483、UMSCC-1和Cal33。

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

48 h;在8个不同HNSCC细胞系中的IC50范围介于58.9-185.7 nM之间。

应用

在8个不同HNSCC细胞系中,台盼蓝染色试验测得ONX 0912的IC50范围介于58.9-185.7 nM之间。在4个HNSCC细胞系(UMSCC-1、UMSCC-22B、1483和UMSCC-1)中,ONX 0912导致caspase-3加工成其活性亚基,以及caspase底物PARP的裂解。

动物实验:

动物模型

无胸腺裸鼠

剂量

30 mg/kg;口服给药

应用

在HNSCC异种移植裸鼠中,ONX 0912以30 mg/kg的剂量口服给药后有效抑制正常组织和HNSCC肿瘤组织的CT-L活性。ONX 0912以10 mg/kg和30 mg/kg的剂量口服给药,1次/天,连续2天,每周重复,重复2周。与对照相比,10 mg/kg ONX 0912对肿瘤的生长没有显著的效应。相比之下,30 mg/kg ONX 0912显著抑制HNSCC肿瘤的生长(P = 0.003)。这些结果表明,ONX 0912以显示良好耐受性的剂量通过口服的方式连续天给药可以抑制HNSCC肿瘤的生长。

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] Zang Y, Thomas S M, Chan E T, et al. Carfilzomib and ONX 0912 inhibit cell survival and tumor growth of head and neck cancer and their activities are enhanced by suppression of Mcl-1 or autophagy[J]. Clinical Cancer Research, 2012, 18(20): 5639-5649.

生物活性

描述 Oprozomib (ONX 0912)是一种可口服的和有效的20S蛋白酶体β5/LMP7的胰凝乳蛋白酶(CT-L)样活性抑制剂,IC50值分别为36 nM和82 nM。
靶点 20S proteasome β5 20S proteasome LMP7        
IC50 36 nM 82 nM        

质量控制

化学结构

Oprozomib (ONX-0912)

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Oprozomib (ONX-0912)

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Oprozomib (ONX-0912)

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Oprozomib (ONX-0912)

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Oprozomib (ONX-0912)