Mirdametinib (PD0325901)

Pfizer辉瑞授权 目录号:S1036

仅限科研使用

Mirdametinib (PD0325901) 是一种选择性的,非ATP竞争性MEK抑制剂,无细胞试验中IC50为0.33 nM,对ERK1和ERK2磷酸化抑制作用比CI-1040强500倍左右。Phase 2。

Mirdametinib (PD0325901) Chemical Structure

CAS: 391210-10-9

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 1149.21 现货
RMB 580.85 现货
RMB 2226.87 现货
RMB 6305.45 现货
大包装 有超大折扣

今日订购,明日送达 全国免运费 分装免费 分装成小规格产品(单支最小为1mg)
如1支10mg产品可分装为10支1mg产品

全国免费电话:400-668-6834   |   Email:info@selleck.cn

客户使用Selleck生产的Mirdametinib (PD0325901)发表文献670篇:

产品安全说明书

MEK抑制剂选择性比较

相关MEK产品

生物活性

产品描述 Mirdametinib (PD0325901) 是一种选择性的,非ATP竞争性MEK抑制剂,无细胞试验中IC50为0.33 nM,对ERK1和ERK2磷酸化抑制作用比CI-1040强500倍左右。Phase 2。
靶点
MEK [1]
(Cell-free assay)
0.33 nM
体外研究

PD0325901比另一种MEK抑制剂CI-1040具有更高的渗透率。与CI-1040相比,PD 0325901可以到达体系的更深层。[1]PD0325901是非ATP竞争性的MAPK激酶MEK抑制剂,抑制鼠类结肠26细胞的MEK时IC50为0.33nM。苏氨酸/酪氨酸激酶MEK是RAS/RAF/MEK/ERK信号通路的关键组成部分,在人类肿瘤细胞中通常是激活的。PD0325901精确有效地抑制MEK,作用于MEK1和MEK2时Ki值为1nM。PD0325901作用于细胞ERK1和ERK2的磷酸化效果比CI-1040强到大约500倍。[2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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HeLa NELKXmlEd26lZX70doF1cW:wLXTldIVv\GWwdDDpcohq[mm2aX;uJI9nKEWUS{WgdIhwe3Cqb4L5cIF1cW:wIIPobYZ1KGmwIFXHSk1{fGmvdXzheIVl NFXMNGJEd26lZX70doF1cW:wLXTldIVv\GWwdDDpcohq[mm2aX;uJI9nKEWUS{WgdIhwe3Cqb4L5cIF1cW:wIIPobYZ1KGmwIFXHSk1{fGmvdXzheIVlKEinTHGgZ4VtdHN? MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzh3MEKxOEc,OTd6NUCyNVQ9N2F-
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rhabdomyosarcoma MVPJcohq[mm2aX;uJI9nKE2HS{GgdIhwe3Cqb4L5cIF1cW:wIHnuJIh2dWGw MWWwMlQhfG9iMUCgeW0> M{XTPFEhcHJ? M3m3VGlvcGmkaYTpc44hd2ZiTVXLNUBxcG:|cHjvdplt[XSrb36gbY4hcHWvYX6gdohi[mSxbYnvd4Fz[2:vYTDj[YxteyCrbn\lZ5Rm\CC5aYToJGVXPzFiQlOwPEBIXTR5NUGyO{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGVTUzFxMjDwbI9{eGixconsZZRqd25iYYSgNE41KHSxIEGwJJVOKHC{ZT30doVifGWmIH\vdkAyKGi{IH\vcIxwf2WmIHL5JJZqemGuIHnu[oVkfGmxbjDt[YF{fXKnZDDh[pRmeiB{NDDodpMh[nlid3XzeIVzdiCkbH;0eIlv\w>? Mn;6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd{OEixPFYoRjJ5Mki4NVg3RC:jPh?=
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Assay
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
体内研究 PD0325901阻止细胞黑色素瘤细胞系的生长,使异种移植鼠模型的细胞周期停止在G1期,引起细胞凋亡单独口服25 mg/kg PD032590124后,ERK的磷酸化作用被阻断达到50%以上。PD 0325901的抗癌活性已经被用于更广泛的人类移植瘤的研究中,在研究的人类肿瘤模型中,有6/7被PD 0325901明显抑制。[2] PD0325901抑制恶性黑色素瘤细胞系生长。PD0325901抑制TPC-1细胞和K2细胞生长,GI50分别为11和6.3 nM。PD0325901浓度非常低时(10 nM)也明显抑制携带BRAF突变的PTC细胞生长,且同样浓度时只稍微提高携带RET/PTC1重排的PTC细胞生长。PD0325901作用于多种PTC细胞系,有效抑制ERK1/2磷酸化。[3]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:

[1]

  • 体外级联实验:

    在有含p44MAPK(GST-MAPK)的谷胱甘肽S-转移酶融合蛋白和含p45MEK(GST-MEK)的谷胱甘肽S-转移酶融合蛋白存在情况下,测定32P渗透到髓鞘碱性蛋白(MBP)的渗透率。实验溶液包括20 mM HEPES,pH 为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,和40 mg MBP,终体积为100 mL。实验进行20分钟后,加入三氯乙酸终止反应,然后通过GF/C过滤器过滤。使用1205 Beta板测定保留在过滤器中的32P。测定不同剂量PD0325901,绘制剂量反应曲线。

细胞实验:

[3]

  • Cell lines: PTC细胞
  • Concentrations: 0.1 nM- 1 μM
  • Incubation Time: 48小时
  • Method:

    1×104个PTC细胞接种在含1mL培养基的24孔板上,在37oC下温育4天。在实验第一天加入不同浓度MEK抑制剂,重复三次。MTT溶于0.8% NaCl溶液,浓度为5 mg/mL,实验第三天,每孔加入0.2 mL,测定GI50或者测定每天的细胞生长曲线。细胞和MTT在37oC下温育3小时。然后从孔中吸出液体除去。染色的细胞溶于0.5 mL DMSO,然后使用Synergy HT增殖酶标仪在570 nm处测定吸光值。然后测定GI50, 按公式 100×(T − T0)/(C − T0)计算细胞生长。

动物实验:

[3]

  • Animal Models: 携带PTC细胞的Ncr-nu/nu鼠
  • Dosages: 20-25 mg/kg
  • Administration: 口服饲喂

溶解度(25°C)

体外

体内

从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
5%DMSO+40%PEG300+5%Tween80+50%ddH2O

5mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 482.19
化学式

C16H14F3IN2O4

CAS号 391210-10-9
储存条件 3年 -20°C 粉状
2年 -80°C 溶于溶剂

动物体内配方计算器(澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)

mg/kg g μL

第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)

% DMSO % % Tween 80 % ddH2O
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

摩尔浓度计算器

质量 浓度 体积 分子量

临床试验信息

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)

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常见问题及建议解决方法

问题 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/