Selumetinib (AZD6244)

目录号:S1008 别名: ARRY-142886 中文名称:司美替尼

仅限科研使用

Selumetinib (AZD6244, ARRY-142886)是一种有效,高选择性的MEK抑制剂,对MEK1的IC50为14 nM,对MEK2的Kd值为530 nM。它也抑制ERK1/2磷c酸化,IC50为10 nM,对p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf等没有抑制作用。Selumetinib可抑制细胞增殖、迁移并诱导凋亡。Phase 3。

Selumetinib (AZD6244) Chemical Structure

CAS: 606143-52-6

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 956.17 现货
RMB 741.25 现货
RMB 1395.14 现货
RMB 3011.75 现货
大包装 有超大折扣
大剂量询单有大折扣!

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Selumetinib (AZD6244)发表文献605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 Selumetinib (AZD6244, ARRY-142886)是一种有效,高选择性的MEK抑制剂,对MEK1的IC50为14 nM,对MEK2的Kd值为530 nM。它也抑制ERK1/2磷c酸化,IC50为10 nM,对p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf等没有抑制作用。Selumetinib可抑制细胞增殖、迁移并诱导凋亡。Phase 3。
特性 AZD6244是第一个处于随机二期研究的MEK抑制剂。
靶点
MEK1 [1]
(Cell-free assay)
MEK1 [13]
(Cell-free assay)
MEK2 [13]
(Cell-free assay)
14 nM 99 nM(Kd) 530 nM(Kd)
体外研究

AZD6244是ATP非竞争性的抑制剂,在IC50浓度小于40 nM时使ERK1/2的磷酸化作用失活。AZD6244也通过抑制ERK1/2和p90RSK的磷酸化抑制原代HCC细胞的生长,同时伴随着caspase-3和caspase-7分裂的加强, 及断裂的聚腺苷二磷酸核糖聚合酶的增多。AZD6244在P38,JNK,PI3K,及MEK5/ERK5通路中的作用不大。[1]AZD6244对感知乳腺癌细胞系中的raf突变和非小细胞肺癌细胞系中的ras突变很灵敏。[2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CHP-212 M{nMNWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MY\Jcohq[mm2aX;uJI9nKGi3bXHuJGNJWC1{MUKgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFAvODB|MUWzJO69VS5? MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOlE1PzBzLze+V2FPT0WUPD;hQi=>
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HL-60 M1T2Smdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NVPweHZEUW6qaXLpeIlwdiCxZjDoeY1idiCKTD22NEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOC5yMkS1PUDPxE1w NYrie4c4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTZzNEewNU8oRlODTlfFVlww[T5?
NOMO-1 M4P5XWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M{LPUGlvcGmkaYTpc44hd2ZiaIXtZY4hVk:PTz2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjB|MUm3JO69VS5? MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOlE1PzBzLze+V2FPT0WUPD;hQi=>
DU-4475 MoCxS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MkH6TY5pcWKrdHnvckBw\iCqdX3hckBFXS12NEe1JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjB|M{[3JO69VS5? NE\zTJg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyPjF2N{CxM{c,W0GQR1XSQE9iRg>?
M14 NHPTTJdIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NWLlSFFuUW6qaXLpeIlwdiCxZjDoeY1idiCPMUSgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFAvODN4OEmg{txONg>? MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOlE1PzBzLze+V2FPT0WUPD;hQi=>
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C32 M3rYcWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MX\Jcohq[mm2aX;uJI9nKGi3bXHuJGM{OiClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxKD1iMD6wPVgzOyEQvF2u M4juV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE3OTR5MEGvK|5USU6JRWK8M4E,
BHT-101 NEPB[lFIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MVjJcohq[mm2aX;uJI9nKGi3bXHuJGJJXC1zMEGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFAvOTB4OUOg{txONg>? MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOlE1PzBzLze+V2FPT0WUPD;hQi=>
KY821 NI\4dHpIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MUXJcohq[mm2aX;uJI9nKGi3bXHuJGt[QDJzIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTBiPTCwMlExPzF6IN88UU4> MmDtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVYyPDdyMT:nQnNCVkeHUkyvZV4>
CP50-MEL-B M1Tm[mdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NF7OcYRKdmirYnn0bY9vKG:oIHj1cYFvKEOSNUCtUWVNNUJiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OCB;IECuNVI4QTRizszNMi=> MnjkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVYyPDdyMT:nQnNCVkeHUkyvZV4>
MEL-HO M{\XTWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MXrJcohq[mm2aX;uJI9nKGi3bXHuJG1GVC2KTzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyIE2gNE4yOzh6NDFOwG0v NH;uN|Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyPjF2N{CxM{c,W0GQR1XSQE9iRg>?
EoL-1-cell NVjiN|J3T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MWXJcohq[mm2aX;uJI9nKGi3bXHuJGVwVC1zLXPlcIwh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDBwMUS0O|Yh|ryPLh?= MoXJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVYyPDdyMT:nQnNCVkeHUkyvZV4>
DOK MkTLS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? Mke0TY5pcWKrdHnvckBw\iCqdX3hckBFV0tiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OCB;IECuNVQ4ODhizszNMi=> NFTYUJA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyPjF2N{CxM{c,W0GQR1XSQE9iRg>?
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BPH-1 MknoS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MkjUTY5pcWKrdHnvckBw\iCqdX3hckBDWEhvMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyIE2gNE4yQDJ|MTFOwG0v MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOlE1PzBzLze+V2FPT0WUPD;hQi=>
HuP-T4 M13iRWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MkHQTY5pcWKrdHnvckBw\iCqdX3hckBJfVBvVESgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFAvOTl3M{Kg{txONg>? NYrldnQ4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTZzNEewNU8oRlODTlfFVlww[T5?
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A549 M4D1dWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M1W4c2lvcGmkaYTpc44hd2ZiaIXtZY4hSTV2OTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyIE2gNE4zOTRzMzFOwG0v NX;vTphQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTZzNEewNU8oRlODTlfFVlww[T5?
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Assay
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
体内研究 活体研究显示AZD6244在2-1318, 5-1318, 及26-1004 4-1318移植物中明显抑制ERK1/2的磷酸化,并且在原代2-1318细胞中通过激活caspase通路诱导细胞凋亡。[1]HT-29移植瘤是携带B-raf突变的直肠瘤模型,AZD6244 在100mg/kg剂量时可以抑制HT-29移植瘤中肿瘤的增长,并且AZD6244作用下的肿瘤指数比吉西他滨作用下的肿瘤指数要好[3]。另外,AZD6244可以抑制HCC移植瘤的增长,HCC移植瘤的增长与细胞凋亡的增多,及细胞周期调控的减量调节有关。包括:cyclin D1, cdc-2, CDK 2 ,CDK4, cyclin B1, 及 c-Myc。[4]

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:

[3]

  • 激酶实验:

    在杆状病毒感染的hi5昆虫细胞中表达的组成型的氮端用六聚组氨酸标记的MEK1,通过金属亲和层析、离子交换及凝胶过滤纯化。MEK1的活性评估通过测量[γ-33P]ATP 作用于ERK2的示踪[γ-33P]磷酸的渗透率。实验在96孔板中进行,保温混合物由25 mM HEPES (pH 7.4), 10 mM MgCl2, 5 mM β-甘油磷酸 100 μM 原钒酸钠, 5 mM DTT, 5 nM MEK1, 1 μM ERK2, 和AZD6244 (溶解在 1% DMSO)组成。加入10 μM ATP (0.5 μC k[γ-33P]ATP/每孔)反应开始,然后在室温下温育45分钟。加入同等量的25%的三氯乙酸反应停止,使蛋白沉淀。沉淀的蛋白加到玻璃纤维过滤板上,用0.5%的磷酸冲洗掉过量的示踪ATP,然后在液体闪烁计数管中计算放射性。通过在反应混合物中改变ATP的量来决定ATP相关性。

细胞实验:

[1]

  • Cell lines: 原代HCC细胞系包括2-1318, 4-1318和26-1004细胞
  • Concentrations: 10 μM 左右
  • Incubation Time: 24或48小时
  • Method:

    肿瘤细胞按2.0×104密度接种,温育48小时,然后用培养基清洗细胞两次。用不同浓度的AZD6244处理细胞24小时或者48小时。细胞活力通过MTT实验来测定。用溴脱氧核苷尿嘧啶试剂盒测定细胞增殖。

动物实验:

[1]

  • Animal Models: 携带HCC移植瘤的SCID鼠
  • Dosages: 50或100mg/kg
  • Administration: 口服处理

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):
4% DMSO+30% PEG 300+5% Tween 80+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 457.68
化学式

C17H15BrClFN4O3

CAS号 606143-52-6
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
NCT05101148 Recruiting Drug: Selumetinib Neurofibromatosis Type 1 AstraZeneca|Merck Sharp & Dohme Corp. 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 Corp. December 16 2020 Phase 1
NCT03433183 Recruiting Drug: Selumetinib|Drug: Sirolimus Malignant Peripheral Nerve Sheath Tumors|Neurofibromatosis 1 Sarcoma Alliance for Research through Collaboration|United States Department of Defense|AstraZeneca October 2 2019 Phase 2
NCT03326388 Recruiting Drug: Selumetinib Neurofibromatosis Type 1|Plexiform Neurofibroma|Optic Nerve Glioma Great Ormond Street Hospital for Children NHS Foundation Trust|AstraZeneca September 26 2019 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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常见问题及建议解决方法

问题 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.