AZD6244 (Selumetinib)

製品コードS1008 バッチS100833

印刷

化学情報

Chemical Structure Synonyms ARRY-142886 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H15BrClFN4O3
分子量 457.68 CAS No. 606143-52-6
Solubility (25°C)* 体外 DMSO 91 mg/mL (198.82 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Selumetinib (AZD6244, ARRY-142886) は、MEK1に対するIC50が14 nM、MEK2に対するKd値が530 nMである強力かつ高選択的なMEK阻害剤です。また、ERK1/2リン酸化をIC50 10 nMで阻害しますが、p38α、MKK6、EGFR、ErbB2、ERK2、B-Rafなどに対しては阻害しません。Selumetinibは細胞増殖、遊走を抑制し、apoptosisを誘発します。第3相。
in vitro

Selumetinib (AZD6244) is not competitive with ATP and inactivates the ERK1/2 phosphorylation with IC50 concentrations below 40 nM. It 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. This compound has little effects on the p38, c-Jun-NH2-kinase, phosphatidylinositol 3-kinase, and MEK5/ERK5 pathways. It is sensitive to Raf mutations in breast cancer cell lines and Ras mutations in NSCLC cell lines.

in vivo

Selumetinib (AZD6244) 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. It 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 this compound is better. Otherwise it 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.

特徴 First MEK inhibitor being tested in Phase II clinical trials.

プロトコル(参考用のみ)

キナーゼアッセイ Assay of MEK Kinase Activity
Selumetinib (AZD6244) 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.
細胞アッセイ 細胞株 Primary HCC cell lines including 2-1318, 4-1318 and 26-1004 cells
濃度 ~ 10 μM
反応時間 24 or 48 hours
実験の流れ

Cells are seeded at a density of 2.0 × 104. After 48 hours incubation, the cells are rinsed twice with culture media. They are then treated with various concentrations of Selumetinib (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.
動物実験 動物モデル HCC xenografts in mice homozygous for the SCID (severe combined immunodeficiency) mutation
投薬量 50 or 100mg/kg
投与方法 Administered via p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/17237274/
  • https://pubmed.ncbi.nlm.nih.gov/20587667/
  • https://pubmed.ncbi.nlm.nih.gov/17332304/
  • https://pubmed.ncbi.nlm.nih.gov/17876044/
  • https://pubmed.ncbi.nlm.nih.gov/17699718/
  • https://pubmed.ncbi.nlm.nih.gov/22173548/
  • https://pubmed.ncbi.nlm.nih.gov/22641227/
  • https://pubmed.ncbi.nlm.nih.gov/18381570/
  • https://pubmed.ncbi.nlm.nih.gov/19915144/
  • https://pubmed.ncbi.nlm.nih.gov/18676837/
  • https://pubmed.ncbi.nlm.nih.gov/19910069/
  • https://pubmed.ncbi.nlm.nih.gov/21385921/
  • https://pubmed.ncbi.nlm.nih.gov/22037378/

カスタマーフィードバック

Data from [Oncogene, 2012, 31, 3277–3286]

Data from [Nature, 2010, 468, 968-972]

Data from [Nature, 2010, 468, 973-977]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells [ Nat Commun, 2025, 16(1):4884] PubMed: 40419504
A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] PubMed: 40147445
GCLM lactylation mediated by ACAT2 promotes ferroptosis resistance in KRASG12D-mutant cancer [ Cell Rep, 2025, 44(6):115774] PubMed: 40503938
Targeting LINC02320 prevents colorectal cancer growth via GRB7-dependent inhibition of MAPK signaling pathway [ Cell Mol Biol Lett, 2025, 30(1):86] PubMed: 40691533
Methylstat sensitizes ovarian cancer cells to PARP-inhibition by targeting the histone demethylases JMJD1B/C [ Cancer Gene Ther, 2025, 10.1038/s41417-025-00874-z] PubMed: 39915607
Fibroblasts Attenuate Anti-Tumor Drug Efficacy in Tumor Cells via Paracrine Interactions with Tumor Cells in 3D Plexiform Neurofibroma Cultures [ Cells, 2025, 14(16)1276] PubMed: 40862755
Basroparib overcomes acquired resistance to MEK inhibitors by inhibiting Wnt-mediated cancer stemness in KRAS-mutated colorectal cancer [ Biochem Pharmacol, 2025, 235:116842] PubMed: 40024348
Molecular Evidence Supporting MEK Inhibitor Therapy in NF1 Pseudarthrosis [ J Bone Joint Surg Am, 2025, 107(10):1098-1106] PubMed: 40168468
Oncogenic KRAS Mutations Confer a Unique Mechanotransduction Response to Peristalsis in Colorectal Cancer Cells [ Mol Cancer Res, 2025, 23(2):128-142] PubMed: 39485528
Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials [ J Biomed Mater Res A, 2025, 113(3):e37885] PubMed: 39995146

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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