AZD6244 (Selumetinib)
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.
AZD6244是一种高效和高选择性的MEK1/2抑制剂,作用于MEK1,IC50值为14.1 nM[1]。
AZD6244是第二代MEK1/2抑制剂。在放射性实验中,AZD6244以非ATP竞争的方式有效地抑制纯化的MEK1。AZD6244是一种选择性抑制剂,对其它的酪氨酸激酶(MKK6、EGFR、ErbB2和B-Raf等)没有明显的抑制效果。在细胞实验中,AZD6244抑制MEK1/2的直接底物ERK1/2的磷酸化,IC50值为10.3 nM。在A431细胞中,AZD6244也可以抑制EGF诱导的ERK1/2而非ERK5的磷酸化。由于MEK在细胞增殖中具有重要作用,在包含活化B-Raf 和Ras突变的细胞系中,AZD6244抑制MEK1/2从而抑制细胞生长,IC50范围介于59-473 nM之间。在HT-29异种移植和BxPC3胰腺癌异种移植模型中,AZD6244显著抑制肿瘤生长[1]。
参考文献:
[1] Yeh TC, Marsh V, Bernat BA, Ballard J, Colwell H, Evans RJ, Parry J, Smith D, Brandhuber BJ, Gross S, Marlow A, Hurley B, Lyssikatos J, Lee PA, Winkler JD, Koch K, Wallace E. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res. 2007 Mar 1;13(5):1576-83.
- 1. Alain Aguilar-Valdes, Lilia G. Noriega, et al. "SWATH-MS proteomics of PANC-1 and MIA PaCa-2 pancreatic cancer cells allows identification of drug targets alternative to MEK and PI3K inhibition." Biochem Biophys Res Commun. 2021 Mar 16;552:23-29. PMID:33740661
- 2. Augustin Le Naour, Mélissa Prat, et al. "Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors." Journal of Molecular Cell Biology. 03 September 2019.
- 3. Bunda S, Heir P, et al. "CIC protein instability contributes to tumorigenesis in glioblastoma." Nat Commun. 2019 Feb 8;10(1):661. PMID:30737375
- 4. Khan IA, Yoo BH, et al. "Mek activity is required for ErbB2 expression in breast cancer cells detached from the extracellular matrix." Oncotarget. 2017 Oct 31;8(62):105383-105396. PMID:29285258
- 5. Sieber J, Wieder N, et al. "GDC-0879, a BRAF(V600E) Inhibitor, Protects Kidney Podocytes from Death." Cell Chem Biol. 2017 Dec 6. PMID:29249695
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 457.69 |
Cas No. | 606143-52-6 |
Formula | C17H15BrClFN4O3 |
Solubility | ≥22.88 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
Chemical Name | 6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide |
SDF | Download SDF |
Canonical SMILES | CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO |
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[1]: | |
细胞系 |
1205Lu细胞(BRAFV600E) |
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 |
3 μM;24小时 |
应用 |
AZD6244诱导可逆的G1期细胞周期停滞,从而抑制细胞生长。贴壁1205Lu细胞用DMSO或3 μM AZD6244处理24 h或处理24 h后去除药物再培养24 h,细胞进入G1期细胞周期停滞,但当药物去除后,其重新进入S期。 |
动物实验[2]: | |
动物模型 |
植入HT-29人结肠癌的裸鼠 |
剂量 |
10、25、50或100 mg/kg,2次/天,21天;口服给药 |
应用 |
AZD6244在所有测试剂量下有效抑制肿瘤生长。两个最高剂量组到达肿瘤生长终点的时间是36天,而对照组是18天。在10 mg/kg的低剂量组和100 mg/kg的高剂量组,AZD6244给药11天后分别抑制55%和70%的肿瘤生长。停止给药后观察到肿瘤生长的恢复。在100 mg/kg剂量组,肿瘤的再生长显著延迟。 |
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] Haass N K, Sproesser K, Nguyen T K, et al. The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clinical Cancer Research, 2008, 14(1): 230-239. [2] Yeh T C, Marsh V, Bernat B A, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clinical Cancer Research, 2007, 13(5): 1576-1583. |
描述 | Selumetinib (AZD6244)是一种有效的和高选择性的MEK1抑制剂,IC50值为14 nM。 | |||||
靶点 | MEK1 | |||||
IC50 | 14 nM |
质量控制和MSDS
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