CX-5461
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.
CX-5461是一种有效的和可口服的rRNA合成的小分子抑制剂,特异性抑制RNA聚合酶(Pol)I介导的转录,IC50值为142 nM。在人胰腺癌细胞MIA Paca-2、人黑色素瘤细胞A375和大肠癌细胞HCT-116中,CX-5461具有抗增殖活性,EC50值分别为74、58和167 nmol/L[1]。
CX-5461通过促进p53的稳定,从而抑制Pol I介导的转录。此外,在MIA Paca-2和A375细胞系中,CX-5461诱导自噬和衰老,而非细胞凋亡。
在MIA Paca-2和A375异种移植小鼠模型中,CX-5461抑制肿瘤生长[1]。
参考文献:
[1] Drygin D1,?Lin A,?Bliesath J,?Ho CB,?O'Brien SE,?Proffitt C,?Omori M,?Haddach M,?Schwaebe MK,?Siddiqui-Jain A,?Streiner N,?Quin JE,?Sanij E,?Bywater MJ,Hannan RD,?Ryckman D,?Anderes K,?Rice WG. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res.?2011 Feb 15;71(4):1418-30
- 1. Zonneville J, Wong V, et al. "TAK1 signaling regulates p53 through a mechanism involving ribosomal stress." Sci Rep. 2020 Feb 13;10(1):2517. PMID:32054925
- 2.Rossetti S, Wierzbicki AJ, et al. "Undermining ribosomal RNA transcription in both the nucleolus and mitochondrion: an offbeat approach to target MYC-driven cancer." Oncotarget. 2017 Dec 22;9(4):5016-5031. PMID:29435159
- 3.Rossetti S, Wierzbicki AJ, et al. "Mammary epithelial morphogenesis and early breast cancer. Evidence of involvement of basal components of the RNA Polymerase I transcription machinery." Cell Cycle. 2016 Aug 2:0. PMID:27485818
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 513.61 |
Cas No. | 1138549-36-6 |
Formula | C27H27N7O2S |
Synonyms | CX 5461;CX5461 |
Solubility | insoluble in H2O; insoluble in EtOH; insoluble in DMSO |
Chemical Name | 2-(4-methyl-1,4-diazepan-1-yl)-N-[(5-methylpyrazin-2-yl)methyl]-5-oxo-[1,3]benzothiazolo[3,2-a][1,8]naphthyridine-6-carboxamide |
SDF | Download SDF |
Canonical SMILES | CC1=CN=C(C=N1)CNC(=O)C2=C3N(C4=CC=CC=C4S3)C5=C(C2=O)C=CC(=N5)N6CCCN(CC6)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 |
hTERT永生化BJ-hTERT人成纤维细胞,人炎性乳腺癌细胞系SUM 149PT和SUM 190PT,人嗜酸性白血病细胞系EOL-1,人B细胞前体白血病细胞系SEM和人急性单核细胞白血病细胞系THP-1 |
制备方法 |
在室温下作为10 mmol/L储备液溶于在50 mmol/L NaH2PO4?(pH 4.5) |
反应条件 |
2 μmol/L, 1 hour |
适用范围 |
用2 μmol/L CX-5461处理HCT-11、A375或MIA PaCa-2将Pol I酶与rDNA启动子的缔合减少40%至60%。在HCT-116细胞中,CX-5461显著减少了Pol I转录因子(TF)与rDNA启动子的结合。在A375和MIA PaCa-2细胞系中,CX-5461抑制DNA合成的IC50范围为16.8至27.9 μmol/L。在实体瘤细胞系中,CX-5461选择性抑制rRNA合成,诱导细胞衰老和自噬。CX-5461靶向Pol I复合物的SL1转录因子,并在实体瘤细胞系中诱导自噬和衰老,相对于正常细胞其选择性地杀死癌细胞。 |
动物实验: [1] | |
动物模型 |
人胰腺癌(MIA PaCa-2)和黑素瘤(A375)的鼠异种移植模型, |
给药剂量 |
口服,50 mg/kg,一天一次或三天一次 |
应用范围 |
在人黑素瘤癌(A375)的鼠异种移植模型中,在第32天,CX-5461产生明显的TGI,TGI等于79%。在鼠异种移植模型中生长的人实体瘤显示CX-5461可以口服给药,具有有利的药代动力学和抗肿瘤功效。 CX-5461耐受性良好,动物体重没有明显变化且明显的毒性作用。 |
其他注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: 1. Drygin D, Lin A, Bliesath J, et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth[J]. Cancer research, 2011, 71(4): 1418-1430. |
描述 | CX-5461是rRNA合成的抑制剂,作用于Pol I介导的rRNA的转录,IC50值为142 nM。 | |||||
靶点 | Pol I | HCT-116 | A375 | MIA PaCa-2 | ||
IC50 | 142 nM | 167 nM (ED50) | 58 nM (ED50) | 74 nM (ED50) |
质量控制和MSDS
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