Pimasertib (AS-703026)

製品コードS1475 別名:MSC1936369B, SAR 245509

Pimasertib (AS-703026)化学構造

分子量(MW):431.20

Pimasertib (AS-703026)は一種の高度選択性的で、有効で、ATP非競争性的なMEK1/2構造変容阻害剤で、MM細胞の中にIC50値が5 nM-2μMです。臨床2期。

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カスタマーフィードバック(3)

  • Western blot analysis showing HSP27 up-regulation on treatment of MKN-45 cells with the 2 indicated MEK1/2 kinase inhibitors (AS703026: 0.5 uM; PD98059: 10 uM) for the indicated time. Inset: effectiveness of the inhibitors in reducing Erk1/2 phosphorylation.

    FASEB J 2014 10.1096/fj.13-247924. Pimasertib (AS-703026) purchased from Selleck.

    GH+E2-induced ERK phosphorylation was examined by Western Blot in T47D cells pre-treated with increasing doses of AS703026.

    Endocrinology 2013 154(9), 3219-27. Pimasertib (AS-703026) purchased from Selleck.

  • After starved in serum-free medium for 24h, T47D cells incubated with the indicated concentrations of AS703026 for 3h,followed by 20-minute stimolation of 100ng/ml EGF.

    Dr. Zhang of Tianjin Medical University. Pimasertib (AS-703026) purchased from Selleck.

製品安全説明書

MEK阻害剤の選択性比較

生物活性

製品説明 Pimasertib (AS-703026)は一種の高度選択性的で、有効で、ATP非競争性的なMEK1/2構造変容阻害剤で、MM細胞の中にIC50値が5 nM-2μMです。臨床2期。
特性 A novel, highly selective and potent allosteric inhibitor of MEK1/2.
靶点
MEK1/2 (MM cell line) [1]
(Cell-free assay)
5 nM-2 μM
In vitro試験

AS703026 is a novel, selective, orally bioavailable MEK1/2 inhibitor that binds to the distinctive MEK allosteric site and therefore exhibits exquisite kinase selectivity. AS703026 inhibits growth and survival of human multiple myeloma (MM) cells, including U266 and INA-6, with IC50 of 5 nM and 11 nM, respectively. Such an inhibitory effect by AS703026 is mediated by G0-G1 cell cycle arrest and is accompanied by reduced expresson of the MAF oncogene. AS703026 further induces apoptosis via caspase-3 and PARP cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). [1] AS703026 may be an effective therapy in colorectal cancer caused by K-Ras mutation. AS703026 (10 μM) effectively inhibits the ERK pathway, proliferation, and transformation in human DLD-1 colorectal cancer cells what carry a mutant allele of K-Ras (D-MUT). [2]

In vivo試験 AS703026 (15 and 30 mg/kg) significantly inhibits tumor growth in a human plasmacytoma xenograft model of H929 MM cells. This can be correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels. [1] AS703026 (10 mg/kg) inhibits tumor growth, and markedly decreases p-ERK level in a xenograft mouse model of human K-Ras mutated (D-MUT) colorectal tumor. [2]

プロトコル(参考用のみ)

キナーゼアッセイ:[3]
+ 展開

MEK1 enzyme assays:

AS703026 is dissolved in 2.5% DMSO. Activated diphosphorylated MEK (pp-MEK) assays contained 40 μM 33P-γATP (AppKm 8.5 μM), 0.5 nM human-activated MEK1 or MEK2, 1 μM kinase-dead ERK2 (AppKm 0.73 μM). All assays are done in buffer containing 20 mM HEPES (pH 7.2), 5 mM 2-mercaptoethanol, 0.15 mg/mL BSA, and 10 mM MgCl2. The final concentration of 33P- ATP is 0.02 μCi/μL for all the assays. pp-MEK kinase reactions are stopped after 40 min by transferring 30 μL of reaction mixture to Durapore 0.45-μm filters plates containing 12.5% TCA. Filters are dried and read with liquid scintilant on a TopCount. Concentration response data are analyzed for IC50. 0.2 nM recombinant human MEK1 or MEK2 is preincubated with vehicle or with AS703026 for 40 minutes in reaction buffer to determine IC50 of initially unphosphorylated MEK (u-MEK). Phosphorylation/activation is initiated by the addition of a final concentration of 20 nM final B-RafV600E and 30 μM final ATP for 10 min. B-Raf activity is then quenched by addition of the B-Raf inhibitor SB590885 (final concentration 100 nM), and MEK kinase activity is assayed by the addition of 1 μM KD-ERK2 and 0.02 μCi/μL 33P-ATP in reaction buffer. The kinase reactions are stopped after 90 min by transferring 30μL of reaction mixture to a Durapore filter plate, and read as above.
細胞アッセイ: [1]
+ 展開
  • 細胞株: U266 and INA-6 cells
  • 濃度: 2 nM - 20 μM (stock: 10 mM in DMSO)
  • 反応時間: 48 hours
  • 実験の流れ: Cytotoxicity assays for AS703026 are assessed by measuring both [3H]thymidine incorporation and MTT dye absorbance. Cells (1 × 104 per well) are cultured in 96-well plates for 3 days. For the [3H]thymidine incorporation assay, cells are pulsed with 18.5 kBq/well [3H]thymidine for 6 hours, harvested onto glass fibre filters, and counted in a β-scintillation counter. Cell cycle analysis is assessed by propidium iodide (PI) staining using flow cytometry. AS703026-induced apoptosis is determined by annexin-V/PI staining and flow cytometric data analysis.
    (参考用のみ)
動物実験:[1]
+ 展開
  • 動物モデル: H929 MM xenografts are established in CB17 (SCID) mice
  • 製剤: 10 mg/mL, dissolved in 0.5% carboxymethylcellulose / 0.25% Tween20
  • 投薬量: 15 or 30 mg/kg
  • 投与方法: Oral gavage twice daily
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 86 mg/mL (199.44 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
体内 0.5% CMC+0.25% Tween 80 30 mg/mL

* <1 mg/mlは製品が微弱に溶解する或いは溶解しないことを示します。
* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。

化学情報

分子量 431.20
化学式

C15H15FIN3O3

CAS No. 1236699-92-5
保管
in solvent
別名 MSC1936369B, SAR 245509

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01992874 Completed Neoplasms EMD Serono November 2013 Phase 1
NCT01985191 Completed Neoplasm Malignant Sanofi|Merck KGaA November 2013 Phase 1
NCT01936363 Active, not recruiting Ovarian Cancer EMD Serono|Sanofi September 2013 Phase 2
NCT01693068 Completed N-Ras Mutated Locally Advanced or Metastasis Malignant Cutaneous Melanoma EMD Serono|Merck KGaA December 2012 Phase 2
NCT01713036 Completed Locally Advanced or Metastatic Solid Tumors Merck KGaA November 2012 Phase 1
NCT01668017 Terminated Advanced Solid Tumors|Hepatocellular Carcinoma Merck KGaA|Merck Serono Co., Ltd., Japan September 2012 Phase 1

技術サポート

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

Handling Instructions

他の質問がある場合は、お気軽くお問合せください。

  • * 必須

MEK信号経路図

MEK Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID