Selumetinib (AZD6244)

製品コード:S1008 別名:ARRY-142886

For research use only.

Selumetinib (AZD6244, ARRY-142886) is a potent, highly selective MEK inhibitor with IC50 of 14 nM for MEK1 and Kd value of 530 nM for MEK2. It also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Selumetinib suppresses cell proliferation, migration and trigger apoptosis. Phase 3.

Selumetinib (AZD6244)化学構造

CAS No. 606143-52-6

サイズ 価格(税別)
10mM (1mL in DMSO) JPY 21400
JPY 16900
JPY 23500
JPY 30200
JPY 63400

代表番号: 03-5615-9297|電子メール:[email protected]
よく尋ねられる質問

文献中Selleckの製品使用例(614)

製品安全説明書

MEK阻害剤の選択性比較

相関MEK製品

生物活性

製品説明 Selumetinib (AZD6244, ARRY-142886) is a potent, highly selective MEK inhibitor with IC50 of 14 nM for MEK1 and Kd value of 530 nM for MEK2. It also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Selumetinib suppresses cell proliferation, migration and trigger apoptosis. Phase 3.
特性 First MEK inhibitor being tested in Phase II clinical trials.
ターゲット
MEK1 [1]
(Cell-free assay)
MEK1 [13]
(Cell-free assay)
MEK2 [13]
(Cell-free assay)
14 nM 99 nM(Kd) 530 nM(Kd)
体外試験

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. [1] AZD6244 is sensitive to Raf mutations in breast cancer cell lines and Ras mutations in NSCLC cell lines. [2]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CHP-212 M{LoT2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 Moj4TY5pcWKrdHnvckBw\iCqdX3hckBEUFBvMkGyJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjByM{G1N{DPxE1w M1XyeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE3OTR5MEGvK|5USU6JRWK8M4E,
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HL-60 M13hZ2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 Mmq2TY5pcWKrdHnvckBw\iCqdX3hckBJVC14MDDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyIE2gNE4xOjR3OTFOwG0v NVjSWW9mRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTZzNEewNU8oRlODTlfFVlww[T5?
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DU-4475 M1jBNmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MmTITY5pcWKrdHnvckBw\iCqdX3hckBFXS12NEe1JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjB|M{[3JO69VS5? MojuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVYyPDdyMT:nQnNCVkeHUkyvZV4>
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DOK NHPqc3lIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M1u3WGlvcGmkaYTpc44hd2ZiaIXtZY4hTE:NIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTBiPTCwMlE1PzB6IN88UU4> MnrjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVYyPDdyMT:nQnNCVkeHUkyvZV4>
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アッセイ
Methods Test Index PMID
Western blot p-ERK / ERK / β-catenin / E-cadherin / Vimentin / Fibronection ; pS6(235/236) / pS6(240/244) ; pVEGFR(Y1175) / VEGFR2 / pPDGFRβ(Y751) / pPDGFRβ / pAXL(Y702) / AXL / pMEK / MEK ; Bak / Bad / Bcl-xl / BimEL / BimL / BimS / PUMA / NOXA 26384399 26137449 22500798 20885957
Immunofluorescence β-catenin ; FOXO3a 26384399 20885957
Growth inhibition assay Cell viability 26384399
体内試験 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. [1] 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. [3] 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. [4]

お薦めの試験操作(参考用のみ)

キナーゼ試験:

[1]

  • Assay of MEK Kinase Activity:

    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.

細胞試験:

[1]

  • 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. 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.

動物試験:

[1]

  • 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.

溶解度 (25°C)

体外

体内

左から(NMPから)右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ):
4% DMSO+30% PEG 300+5% Tween 80+ddH2O
混合させたのち直ちに使用することを推奨します。

5mg/mL

化学情報

分子量 457.68
化学式

C17H15BrClFN4O3

CAS No. 606143-52-6
Storage 3年 -20°C
2年 -80°C in solvent
Smiles CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

便利ツール

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05253131 Not yet recruiting Drug: Selumetinib MPNST|NF1|Sarcoma University of Alabama at Birmingham|United States Department of Defense October 15 2022 Phase 1|Phase 2
NCT05101148 Active not recruiting Drug: Selumetinib Neurofibromatosis Type 1 AstraZeneca|Merck Sharp & Dohme LLC July 21 2021 Phase 1
NCT04879160 Recruiting -- Neurofibromatosis 1 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) May 12 2021 --
NCT04590235 Active not recruiting Drug: Selumetinib Neurofibromatosis 1|Neurofibroma Plexiform AstraZeneca|Merck Sharp & Dohme LLC December 16 2020 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

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よくある質問(FAQ)

質問1:
How about the solubility of S1008? How to prepare for the solution if I need to do the in vivo experiments?

回答
S1008 AZD6244 in vehicle 5% DMSO+30% PEG 300+ddH2O will be a suspension for oral administration. If you want a clear solution for injection, you can dissolve it in 4% DMSO+30% PEG 300+5% Tween 80+ddH2O.

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