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Selumetinib(AZD-6244 ARRY142886)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Selumetinib(AZD-6244 ARRY142886)图片
CAS NO:606143-52-6
规格:≥98%
包装与价格:
包装价格(元)
100mg电议
250mg电议
500mg电议
1g电议
2g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)457.68
FormulaC17H15BrClFN4O3
CAS No.606143-52-6
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 91 mg/mL (198.8 mM)
Water: <1 mg/mL
Ethanol:<1 mg/mL
Solubility (In vivo)4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5 mg/mL
Synonyms

selumetinib; ARRY-142886; AZD6244; ARRY142886; ARRY 142886; AZD-6244; AZD 6244; ARRY886; ARRY-886; ARRY 886

Chemical Name: 6-[(4-bromo-2-chlorophenyl)amino]-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide

InChi Key: CYOHGALHFOKKQC-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H15BrClFN4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)

SMILES Code: O=C(C1=C(NC2=CC=C(Br)C=C2Cl)C(F)=C3C(N(C)C=N3)=C1)NOCCO

实验参考方法
In Vitro

In vitro activity: AZD6244 is not competitive with ATP and inactivates the ERK1/2 phosphorylation with IC50 concentrations below 40 nM. AZD6244 also inhibits the growth of primary HCC cells through inhibition of ERK1/2 and p90RSK phosphorylation, accompanied with elevation of the cleavage of caspase-3 and caspase-7, and cleaved poly(ADP)ribose polymerase. AZD6244 has little effects on the p38, c-Jun-NH2-kinase, phosphatidylinositol 3-kinase, and MEK5/ERK5 pathways. AZD6244 is sensitive to Raf mutations in breast cancer cell lines and Ras mutations in NSCLC cell lines.


Kinase Assay: Anti-MEK1 antibody is used to immunoprecipitate MEK1 molecules. MEK kinase activity is measured as the ability of immuno-isolated MEK1 to activate recombinant ERK1 in a coupled assay using MBP as the end point of the assay. Phosphorylated MBP is resolved on a 14% SDS-PAGE gel and vacuum-dried before exposure to X-ray film.


Cell Assay: Cells (Primary HCC cell lines including 2-1318, 4-1318 and 26-1004 cells) are seeded at a density of 2.0 × 104. After 48 hours incubation, the cells are rinsed twice with culture media. Cells are treated with various concentrations of AZD6244 for 24 or 48 hours. Cell viability is determined by the 3-(4,5-dimethylthiazol-2y1)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation is assayed using a bromodeoxyuridine kit.

In VivoAZD6244 significantly inhibits phosphorylation of ERK1/2 in 2-1318, 5-1318, 26-1004 and 4-1318 xenografts and induces apoptosis in primary 2-1318 cells by activating the caspase pathway. AZD6244 could inhibit the tumor growth in HT-29 xenograft, which is a colorectal tumor model carrying a B-Raf mutation, at a dose of 100 mg/kg and the tumor growth inhibition of AZD6244 is better than it of Gemcitabine. Otherwise AZD6244 could inhibit HCC xenografts tumor growth, which associated with increased apoptosis and down-regulation of cell cycle regulators, including cyclin D1, Cdc-2, CDK2 and 4, cyclin B1, and c-Myc
Animal modelHCC xenografts in mice homozygous for the SCID (severe combined immunodeficiency) mutation
Formulation & DosageDissolved in water; 50 or 100mg/kg; Oral gavage
References

Mol Cancer Ther. 2007 Jan;6(1):138-46; Clin Cancer Res. 2007 Mar 1;13(5):1576-83.