Afatinib (BIBW2992)

目录号:S1011 中文名称:阿法替尼

仅限科研使用

Afatinib (BIBW2992) 不可逆地抑制EGFR/ErbB,包括EGFR(wt)EGFR(L858R),EGFR(L858R/T790M),ErbB2(HER2)和ErbB4(HER4),在无细胞试验中IC50分别为0.5 nM,0.4 nM,10 nM,14 nM和1 nM。Afatinib可诱导自噬。

Afatinib (BIBW2992) Chemical Structure

CAS: 850140-72-6

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 1964.25 现货
RMB 977.68 现货
RMB 4652.69 现货
RMB 10401.3 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Afatinib (BIBW2992)发表文献332篇:

产品安全说明书

EGFR抑制剂选择性比较

相关EGFR产品

生物活性

产品描述 Afatinib (BIBW2992) 不可逆地抑制EGFR/ErbB,包括EGFR(wt)EGFR(L858R),EGFR(L858R/T790M),ErbB2(HER2)和ErbB4(HER4),在无细胞试验中IC50分别为0.5 nM,0.4 nM,10 nM,14 nM和1 nM。Afatinib可诱导自噬。
靶点
EGFR (L858R) [1]
(Cell-free assay)
EGFR (wt) [1]
(Cell-free assay)
ErbB4 [2]
(Cell-free assay)
EGFR (L858R/T790M) [1]
(Cell-free assay)
HER2 [1]
(Cell-free assay)
0.4 nM 0.5 nM 1 nM 10 nM 14 nM
体外研究

BIBW2992不可逆地抑制EGFR/HER2,在体外作用于野生型EGFR ,L858R突变型EGFR, L858R/T790M 双突变型EGFR,及HER2时IC50分别为0.5, 0.4, 10, 14 nM。在体外实验中,BIBW2992不管作用于野生型EGFR/HER2还是突变型EGFR/HER2都显示出强大的活力,与gefitinib作用于L858R突变型EGFR的活力差不多,但是要比gefitinib 作用于L858R-T790M双突变型EGFR的活力大100倍。在体外,BIBW2992有效抑制所有实验类型细胞的EGFR/HER磷酸化作用。比如人类扁平上皮癌A431细胞系表达的野生型EGFR, 鼠类NIH-3T3细胞转染的野生型HER2 , 以及乳腺癌BT-474细胞系和胃癌NCI-N87细胞系表达的内源性HER2。[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HDLM-2 NWLZOWxST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTBwMEC1O|Ih|ryP MoXFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
KASUMI-1 Mk\FS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFLReJJKSzVyPUCuNFA6OTFizszN NYT1R3V5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
HCC2218 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGrOTYxKSzVyPUCuNFA6QDdizszN M1zzWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK|5USU6JRWK8M4E,
KARPAS-45 M{LVNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2HleGlEPTB;MD6wNVY4OSEQvF2= MmPyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
HSC-4 NHPsS4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3HlO2lEPTB;MD6wNVc1QCEQvF2= Mm[yQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
CHL-1 MonYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MofETWM2OD1yLkCxPFM6KM7:TR?= MmXnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
KY821 M4HHZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTBwMEKwOkDPxE1? M2nV[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK|5USU6JRWK8M4E,
NCI-N87 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MknqTWM2OD1yLkCyO|c{KM7:TR?= MmHxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
DOK M3qzVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{exO2lEPTB;MD6wN|E6PCEQvF2= Mn7jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
DSH1 MknmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV21SndDUUN3ME2wMlA{OzF2IN88US=> MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
MDA-MB-175-VII M3;YcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWrJR|UxRTBwMEO0NVYh|ryP NWnWT3JQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NCI-H2170 MnK1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXyZohKSzVyPUCuNFM4OjhizszN MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
BT-474 M4XmNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEPzWIdKSzVyPUCuNFQ6QDZizszN M{P5SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK|5USU6JRWK8M4E,
EFO-27 NEflOldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVzJR|UxRTBwMEWxPFIh|ryP NWKwOJlsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NCI-H720 NWn4bXYxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWHJR|UxRTBwMEWzNlUh|ryP NYTEO4FPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
PC-14 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXnJR|UxRTBwMEW2Olgh|ryP MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
EC-GI-10 NF:2bZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\aWGZGUUN3ME2wMlA2QTF{IN88US=> NWqxUZN{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
KYSE-450 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnm0TWM2OD1yLkC1PVc5KM7:TR?= NVjReXFsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
BPH-1 MnfhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3THbmlEPTB;MD6wOVk5QCEQvF2= MlLmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
NCI-H292 M4SxeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\CdGlEPTB;MD6wOlA6KM7:TR?= M2HudlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK|5USU6JRWK8M4E,
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NCI-H526 NXHDeJZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7IU|RKSzVyPUCuNFc5OjNizszN NXXI[4xSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NCI-H1623 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LLfWlEPTB;MD6wPFAzPSEQvF2= MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
KYSE-140 NWezcZJIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrhcJQ1UUN3ME2wMlA5OzNizszN NEjRb2c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd|NkW1M{c,W0GQR1XSQE9iRg>?
Ca9-22 MnHLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjhdZFKSzVyPUCuNFg{PTNizszN NUTNOlZGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
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BB30-HNC MmmwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVLJR|UxRTBwMU[1O|Yh|ryP MnSyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
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Assay
Methods Test Index PMID
Western blot CIP2A / p-AKT / AKT / PARP p-EGFR / p-IGF1R / p-ERK / p-AKT p-VEGFR2 / VEGFR2 / JAG1 / DLL4 / NICD1 25537503 26052929 28533486
Growth inhibition assay Cell apoptosis Cell viability 25537503 26515464
Immunofluorescence p65 vacuoles 26317651 29713246
体内研究 活体研究时按实验对象体重,每千克口服20 mg BIBW2992持续25天,肿瘤产生明显的衰退现象,通过肿瘤切片的免疫组织化学染色观察发现,EGFR和AKT的磷酸化作用收到抑制。因此,正如lapatinib和neratinib, BIBW2992是次代酪氨酸激酶抑制剂,不可逆地抑制人类EGFR2(HER2)和EGFR激酶。BIBW2992不仅能和原代酪氨酸激酶如erlotinib和gefitinib一样有效抑制EGFR突变型,而且还能作用于抗erlotinib和gefitinib的EGFR。[1]

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]

  • 体外激酶活性实验:

    人类EGFR和L858R/T790M双重突变型EGFR 的酪氨酸激酶区域与谷胱甘肽巯基转移酶区域相接,提取酪氨酸激酶区域的方法见补充说明。在有和没有BIBW2992时分别测定酶活。使用杆状病毒系统克隆HER2激酶,用类似提取EGFR激酶域的方法提取HER2激酶域。

细胞实验:

[1]

  • Cell lines: NSCLC细胞
  • Concentrations: 0-10 μM
  • Incubation Time: 1小时
  • Method:

    细胞按1×104密度转移到96孔板上,在无血清培养基上过夜培养,用于EGFR磷酸化实验。第二天添加包含BIBW2992的混合物,培养基在37oC温育1小时。在室温下用100 ng/ml EGF刺激10分钟。细胞用冰冻PBS冲洗,然后每孔用120 μl HEPEX buffer萃取,然后在室温下震荡1小时。每孔中所有2×104细胞都用于HER2磷酸化实验。在涂有链霉亲和素的板上加用封闭液按1:100比例稀释的抗EGFR的生物素和c-erb2/HER2肿瘤蛋白Ab-5-生物素。上述步骤得到的萃取物转移到有抗体包被的孔中,室温下温育1小时。彩色显影的测法见补充说明,吸光度为450纳米。

动物实验:

[1]

  • Animal Models: 雌性无胸腺NMRI-nu/nu鼠
  • Dosages: 20 mg/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):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O

10mg/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 485.94
化学式

C24H25ClFN5O3

CAS号 850140-72-6
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
NCT05298176 Recruiting Drug: Afatinib Osimertinib Carboplatin and Pemetrexed Non-Small Cell Lung Cancer Amsterdam UMC location VUmc January 4 2022 Phase 2
NCT04795245 Active not recruiting Drug: afatinib Non-squamous Non-Small Cell Lung Cancer Boehringer Ingelheim August 26 2021 --
NCT04497584 Recruiting Drug: Afatinib + Prednisone Advanced Squamous Non Small Cell Lung Cancer University of Texas Southwestern Medical Center August 4 2021 Phase 2
NCT04413201 Recruiting Drug: Afatinib|Drug: Osimertinib Non-squamous NSCLC Michael Hopp|Boehringer Ingelheim|Johannes Gutenberg University Mainz September 11 2020 Phase 4
NCT04206787 Active not recruiting Drug: Afatinib Non-squamous Non-Small Cell Lung Cancer Boehringer Ingelheim May 20 2020 --

(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:
What’s the recommendation about reconstitution of the compound for in vivo animal study?

回答:
For in vivo experiment of afatinib, we recommend 0.5% methylcellulose/0.2% Tween 80 as vehicle.