RO5126766(CH5126766)
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.
RO5126766(CH5126766)是首创的Raf/MEK双重抑制剂[1].
RAS/RAF/MEK/ERK信号通路是一个重要的信号转导系统,参与细胞分化\运动\分裂和死亡.活化的Ras激活Raf激酶,随后磷酸化和活化MEK(MEK1 和 MEK2)[1].BRAF\RAS和NF1的突变与许多人类肿瘤相关[2].
RO5126766(CH5126766)是首创的Raf/MEK双重抑制剂.在无细胞激酶实验中,CH5126766有效抑制RAF磷酸化MEK1蛋白和MEK1对ERK2蛋白的活化,IC50值分别为0.0082-0.056和0.16 μM.在NCI-H460 (KRAS Q61H)人肺大细胞癌细胞系中,RO5126766诱导细胞周期抑制剂p27Kip1蛋白的表达,造成G1期阻滞.在HCT116 KRAS突变的结直肠癌细胞中,RO5126766 (CH5126766)完全抑制MEK和ERK的磷酸化[2].
在晚期实体瘤日本患者中,RO5126766每日一次,最大耐受剂量(MTD)为2.25 mg/day[1].在HCT116(G13D KRAS)异种移植小鼠模型中,1.5 mg/kg的RO5126766抑制pERK和ERK信号,ED50为0.056 mg/kg[2].
参考文献：
[1]. Honda K, Yamamoto N, Nokihara H, et al. Phase I and pharmacokinetic/pharmacodynamic study of RO5126766, a first-in-class dual Raf/MEK inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol, 2013, 72(3): 577-584.
[2]. Ishii N, Harada N, Joseph EW, et al. Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Res, 2013, 73(13): 4050-4060.
- 1. Wang Z, Zhang Z, et al. "Polysaccharides from Enteromorpha Prolifera Ameliorate Acute Myocardial Infarction in Vitro and in Vivo via Up-Regulating HIF-1α." Int Heart J. 2019 Jun 28. PMID:31257333
- 2. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID:31063758
| Storage | Store at -20°C |
| M.Wt | 471.46 |
| Cas No. | 946128-88-7 |
| Formula | C21H18FN5O5S |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥35.7 mg/mL in DMSO |
| SDF | Download SDF |
| Canonical SMILES | CC(C1=C(O2)C=C(OC3=NC=CC=N3)C=C1)=C(C2=O)CC4=C(F)C(NS(NC)(=O)=O)=NC=C4 |
| 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。 |
| 酶学实验 [1]: | |
|
激酶检测 |
通过与活性MEK1（MEK1 S218E/S222E）和非活性脱磷酸化ERK2（MAP激酶2/Erk 2）的偶联反应测定来评估对MEK1的抑制。通过使用IMAP FP Screening Express试剂盒来定量ERK2催化的荧光标记的肽底物（FAM-Erktide，IPTTPITTTYFFFK-5FAM-COOH）的磷酸化。 |
| 细胞实验 [1]: | |
|
细胞系 |
HCT116细胞系 |
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溶解方法 |
溶于DMSO。为了获得更高浓度，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 |
细胞用CH5126766（250 nmol/L，0.1％DMSO）处理2小时。 |
|
应用 |
CH5126766结合能使MEK蛋白发生构型改变导致其不能被RAF磷酸化，结果就是形成了一个稳定的MEK/RAF复合体并抑制RAF活性。跟这个机制一致的是，CH5126766并不能诱导MEK的磷酸化。 |
| 动物实验 [1]: | |
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动物模型 |
HCT116小鼠异种移植模型 |
|
剂量 |
将CH5126766溶于含有5％DMSO和10％HPCD的蒸馏水中。药物每天口服1.5mg/kg。 |
|
应用 |
在HCT116小鼠异种移植模型中，每日口服CH5126766导致显著的肿瘤消退。 |
|
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。 |
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References: [1] Ishii N, et al. Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Res. 2013 Jul 1;73(13):4050-60. |
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质量控制和MSDS
- 批次:
化学结构
相关生物数据
