Oprozomib (ONX-0912)
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-0912(oprozomib)是在使用三肽环氧酮的药物化学中被发现的,是一种可口服的和有效的蛋白酶体抑制剂,抑制bortezomib抗性多发性骨髓瘤(MM)细胞的生长,诱导细胞凋亡。尽管ONX-0912(carfilzomib的类似物)与bortezomib在结构上截然不同,但与bortezomib具有同样的效力,主要抑制蛋白酶体的胰凝乳蛋白酶样活性。在多个动物肿瘤模型研究中,ONX-0912通过激活caspase-3、caspase-8、caspase-9和聚(ADP)核糖聚合酶(PARP),抑制血管生成和MM细胞迁移,具有显著的抗MM活性,减少肿瘤的发展,延长存活。
参考文献:
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
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- 4. 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
- 5. 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
- 6. 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
Physical Appearance | A solid |
Storage | Desiccate at -20°C |
M.Wt | 532.61 |
Cas No. | 935888-69-0 |
Formula | C25H32N4O7S |
Synonyms | ONX-0912,ONX0912,ONX 0912,PR 047,Oprozomib |
Solubility | ≥26.6 mg/mL in DMSO; insoluble in H2O; ≥2.77 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | N-[(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 |
SDF | Download SDF |
Canonical SMILES | CC1=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 | 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: | |
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. |
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 |
质量控制和MSDS
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