Mirdametinib (PD0325901)

Licensed by Pfizer 製品コード:S1036

For research use only.

Mirdametinib (PD0325901) is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM in cell-free assays, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2.

Mirdametinib (PD0325901)化学構造

CAS No. 391210-10-9

サイズ 価格(税別)
10mM (1mL in DMSO) JPY 25200
JPY 13600
JPY 46800
JPY 129800

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(669)

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 Mirdametinib (PD0325901) is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM in cell-free assays, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2.
ターゲット
MEK [1]
(Cell-free assay)
0.33 nM
体外試験

PD0325901 shows higher permeability than CI-1040, another MEK inhibitor. PD0325901 should be able to achieve higher systemic exposures than CI-1040. [1] PD0325901 is exquisitely specific and highly potent against purified MEK, revealing a Kiapp of 1 nM against activated MEK1 and MEK2. [2] PD0325901 is roughly 500-fold more potent than CI-1040 with respect to its cellular effects on phosphorylation of ERK1 and ERK2, displaying subnanomolar activity. [2] PD0325901 prevents the growth of melanoma cell lines. PD0325901 inhibits the growth of TPC-1 cells and K2 cells with GI50 of 11 nM and 6.3 nM, respectively. [3] PD0325901 significantly prevents the the growth of PTC cells harboring a BRAF mutation at very low concentration (10 nM) and only moderately increases the growth of the PTC cells carrying the RET/PTC1 rearrangement at the same concentration. PD0325901 effectively inhibits the phosphorylation of ERK1/2 in multiple PTC cell lines. [3]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A549 MUHJcohq[mm2aX;uJI9nKE2HS{GgbY4hcHWvYX6= M3j2[VExKHWP NXXzO|A2OSCqch?= NH7aSm5KdmirYnn0bY9vKG:oIF3FT|EhcW5iaIXtZY4hSTV2OTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4heEW{a{GvNkBt\X[nbDDheEAyOCC3TTDh[pRmeiBzIHjyJIJ6KFenc4Tldo4h[myxdITpcoch[W6jbInzbZM> NUOzPXRFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OlY3OzNpPkK1O|Y3PjN|PD;hQi=>
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A549 NXiyO4o6UW6qaXLpeIlwdiCxZjDNSYsyNzJiaX6gbJVu[W5? MUG3OUBucW6| MnnhTY5pcWKrdHnvckBw\iCPRXuxM|IhcW5iaIXtZY4hSTV2OTDj[YxteyCjc4Pld5Nm\CCjczDk[YNz\WG|ZTDpckBGWkticHjvd5Bpd3K7bHH0bY9vKGGodHXyJFc2KG2rboOgZpkhX2W|dHXyckBjdG:2dHnu[{BidmGueYPpdy=> MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN7OES1N{c,OjN|OUi0OVM9N2F-
CCD-1070sk NXnPTmdXUW6qaXLpeIlwdiCxZjDNSYsyNzJiaX6gbJVu[W5? NEfIXWc4PSCvaX7z NEPKXWlKdmirYnn0bY9vKG:oIF3Fb|EwOiCrbjDoeY1idiCFQ1StNVA4OHOtIHPlcIx{KGG|c3Xzd4VlKGG|IHTlZ5Jm[XOnIHnuJGVTUyCyaH;zdIhwenmuYYTpc44h[W[2ZYKgO|UhdWmwczDifUBY\XO2ZYLuJIJtd3S2aX7nJIFv[Wy7c3nz M4HyR|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|M{m4OFU{Lz5{M{O5PFQ2OzxxYU6=
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MCF7 MXTJcohq[mm2aX;uJI9nKE2Ha{GvNkBqdiCqdX3hci=> MXK3OUBucW6| Mnj1TY5pcWKrdHnvckBw\iCPRXuxM|IhcW5iaIXtZY4hVUOINzDj[YxteyCjc4Pld5Nm\CCjczDk[YNz\WG|ZTDpckBGWkticHjvd5Bpd3K7bHH0bY9vKGGodHXyJFc2KG2rboOgZpkhX2W|dHXyckBjdG:2dHnu[{BidmGueYPpdy=> M1LxO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|M{m4OFU{Lz5{M{O5PFQ2OzxxYU6=
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アッセイ
Methods Test Index PMID
Western blot p-ERK / p-AKT / Cyclin D1 / p27 ; p-p70S6K(T389) / p4EBP1(S65) / pS6(S235) ; cleaved PARP ; DR5 22573716 27699948 25867065
Immunofluorescence Fibronectin / Actin / pFAK ; ZO-1 28187762 25394671
体内試験 The improved potency of PD0325901 relative to CI-1040 is evident. A single oral dose of PD0325901 (25 mg/kg) inhibits phosphorylation of ERK by more than 50% at 24 hours post-dosing. In contrast, CI-1040 at a much higher dose (150 mg/kg) only inhibit pERK levels for roughly 8 hours, returning to control levels by 24 hours after treatment. [2] Therefore, the dose required to produce a 70% incidence of complete tumor responses (C26 model) is 25 mg/kg/day versus 900 mg/kg/day for PD0325901 and CI-1040, respectively. Anticancer activity of PD 0325901 has been demonstrated for a broad spectrum of human tumor xenografts. [2] After 1 week of oral administration of PD0325901 (20–25 mg/kg/day) in mice, no tumor growth is detected in mice inoculated with PTC cells bearing a BRAF mutation. [3] For PTC with the RET/PTC1 rearrangement, the average tumor volume of the orthotopic tumor is decreased by 58% as compared with controls. In conclusion, PTC cells carrying a BRAF mutation are more sensitive to PD0325901 than are PTC cells carrying the RET/PTC1 rearrangement. [3]

お薦めの試験操作(参考用のみ)

キナーゼ試験:

[1]

  • In vitro cascade assay:

    Incorporation of 32P into myelin basic protein (MBP) is assayed in the presence of a glutathione S-transferase fusion protein containing p44MAP kinase (GST-MAPK) and a glutathione S-transferase protein containing p45MEK (GST-MEK). The assay solution contained 20 mM HEPES, pH 7.4, 10 mM MgCl2, 1 mM MnCl2, 1 mM EGTA, 50 mM [gamma-32P]ATP, 10 mg GST-MEK, 0.5 mg GST-MAPK and 40 mg MBP in a final volume of 100 mL. Reactions are stopped after 20 minutes by addition of trichloroacetic acid and filtered through a GF/C filter mat. 32P retained on the filter mat is determined using a 1205 Betaplate. PD0325901 is assessed at various dose ranges in order to determine dose response curves.

細胞試験:

[3]

  • 細胞株:PTC cells
  • 濃度: 0.1 nM- 1 μM
  • 反応時間:48 hours
  • 実験の流れ:

    PTC cells (1 × 104) are seeded in 24-well plates with 1 mL of medium for 4 days in a 37 °C incubator. MEK inhibitor PD0325901 at varying concentrations is added to the cells in triplicate on day 0. MTT dissolved in 0.8% NaCl solution at 5 mg/mL is added to each well (0.2 mL) on day 2 to test GI50 or every day for cell growth curves. The cells are incubated at 37 °C for 3 hours with MTT. The liquid is then aspirated from the wells and discarded. Stained cells are dissolved in 0.5 mL of DMSO and their absorption at 570 nm is measured using a Synergy HT multidetection microplate reader. For GI50, cell growth is calculated as 100 × (T − T0)/(C − T0), where T is the optical density of the wells treated with inhibitors after a 48-hour period, T0 is the optical density at time zero, and C is the control optical density with DMSO only.

動物試験:

[3]

  • 動物モデル:Ncr-nu/nu mice bearing PTC cells
  • 投薬量:20-25 mg/kg
  • 投与方法:Oral gavage

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):
5%DMSO+40%PEG300+5%Tween80+50%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 482.19
化学式

C16H14F3IN2O4

CAS No. 391210-10-9
Storage 3年 -20°C
2年 -80°C in solvent
Smiles C1=CC(=C(C=C1I)F)NC2=C(C=CC(=C2F)F)C(=O)NOCC(CO)O

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
NCT02510001 Completed Drug: PF-02341066|Drug: PD-0325901|Drug: Binimetinib Solid Tumor|Colorectal Cancer University of Oxford|Queen''s University Belfast|Oxford University Hospitals NHS Trust|Velindre NHS Trust|University Hospital Antwerp|Hospital Vall d''Hebron|Saint Antoine University Hospital|European Georges Pompidou Hospital|Pfizer|University of Turin Italy|Belfast Health and Social Care Trust|Beaumont Hospital|European Commission|Array BioPharma|University of Paris 5 - Rene Descartes November 2014 Phase 1
NCT02096471 Completed Drug: PD-0325901 Neurofibromatosis Type 1 and Growing or Symptomatic Inoperable PN University of Alabama at Birmingham June 2014 Phase 2
NCT02022982 Active not recruiting Drug: Palbociclib|Drug: PD-0325901 KRAS Mutant Non-Small Cell Lung Cancer|Solid Tumors Dana-Farber Cancer Institute January 2014 Phase 1|Phase 2
NCT01347866 Terminated Drug: PF-05212384|Drug: PD-0325901|Drug: irinotecan Advanced Cancer Pfizer October 2011 Phase 1
NCT00174369 Terminated Drug: PD-0325901 Carcinoma Non-Small-Cell Lung Pfizer November 2005 Phase 2

(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。

* 必須

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よくある質問(FAQ)

質問1:
Whether the inhibitor PD0325901 interacts with other targets other than MEK?

回答
PD0325901 has very high selectivity to MEK. In addition, it can also inhibits VEGF activity according to the reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713590/

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