首页 工具
登录
购物车
(S)-Afatinib

(S)-Afatinib

产品编号 T2303   CAS 439081-18-2
别名: BIBW2992, 阿法替尼

(S)-Afatinib (BIBW2992) 是一种不可逆的 EGFR 家族抑制剂,对 EGFRwt、EGFR (L858R)、EGFR (L858R/T790M)、HER2 和 HER4 的 IC50 分别为 0.5/0.4/10/14/1 nM。

TargetMol的所有产品和服务仅用于科学研究,不能被用于人体,我们也不向个人提供产品和服务。
(S)-Afatinib Chemical Structure
(S)-Afatinib, CAS 439081-18-2
规格 价格/CNY 货期 数量
100 mg ¥ 178 现货
1 mL * 10 mM (in DMSO) ¥ 568 现货
其他形式的 (S)-Afatinib:
产品目录号及名称: (S)-Afatinib (T2303)
点击图片重新获取验证码
选择批次  
纯度: 100%
纯度: 99.96%
纯度: 99.96%
更多批次查询请联系客服
生物活性
化学信息
存储 & 溶解度
参考文献
产品描述 (S)-Afatinib (BIBW2992) is an irreversible EGFR family inhibitor with IC50s of 0.5/0.4/10/14/1 nM for EGFRwt, EGFR (L858R), EGFR (L858R/T790M), HER2, and HER4, respectively.
靶点活性 EGFR (wt):0.5 nM (cell free), EGFR (L858R):0.4 nM (cell free), ErbB4:1 nM (cell free), EGFR (L858R/T790M):10 nM (cell free), HER2:14 nM (cell free)
体外活性 BIBW2992 shows potent activity against wild-type and mutant forms of EGFR and HER2 (IC50s: 0.5, 0.4, 10, 14 nM for EGFRwt, EGFR L858R, EGFR L858R/T790M, and HER2, respectively). In the human breast cancer cell line, treatment with 100 nM BIBW2992 was sufficient to prevent heregulin-stimulated HER3 phosphorylation [1]. Esophageal squamous cell carcinoma (ESCC) cell lines were sensitive to afatinib with IC50 concentrations at lower micromolar range (at 72 hour incubation: HKESC-1 = 0.002 μM, HKESC-2 = 0.002 μM, KYSE510 = 1.090 μM, SLMT-1 = 1.161 μM and EC-1 = 0.109 μM). The phosphorylation of ErbB family downstream effectors such as pAKT, pS6 and pMAPK were significantly inhibited in HKESC-2 and EC-1. Apoptosis was observed in both cell lines at 24 hours after exposure to afatinib [2].
体内活性 Daily oral treatment with BIBW2992 at 20 mg/kg for 25 days resulted in dramatic tumor regression and downregulation of EGFR and AKT phosphorylation. Xenograft tumor formation by the NCIH1975 cell line, expressing EGFR L858R/T790M, was effectively controlled by BIBW2992, with a T/C value of 12% for doses of 20 mg/kg [1]. Afatinib could effectively inhibit HKESC-2 tumor growth in mice without obvious toxicity. Afatinib alone has shown excellent growth inhibitory effect on ESCC in in vivo models [2].
激酶实验 The wild type tyrosine kinase domain of the human EGFR, as well as the EGFR L858R/T790M double mutant, were fused to Glutathione-S-transferase (GST) and extracted as described in Supplementary methods. The L858R mutant was purchased from Upstate. Enzyme activity was then assayed in the presence or absence of serial inhibitor dilutions performed in 50% Me2SO. A random polymer pEY (4:1) from Sigma was used as substrate. Biotinylated pEY was added as a tracer substrate. The kinase domain of HER2 was cloned using baculovirus system and extracted similarly to that of EGFR kinase domain. Detailed procedures for EGFR, HER2, SRC, BIRK and VEGFR2 kinase activity assays are included in Supplementary information [1].
细胞实验 Cells (1×10^4) were transferred into each well of a 96-well plate and cultured over night in serum-free media for EGFR phosphorylation assay. After addition of test compounds on the next day, the plates were then incubated at 37°C for 1 hour. EGF-stimulation was done at 100 ng/ml for 10 min at room temperature. Cells were washed with ice cold PBS before extraction with 120 μl per well HEPEX buffer and shaken for 1 h at room temperature. In all 2×10^4 cells per well was used for HER2 phosphorylation assay. Streptavidin precoated plates were coated with anti-EGFR-biotin at 1:100 dilution with blocking buffer and c-erb2/HER2 oncoprotein Ab-5(Clone N24)-Biotin. Extracts from above steps were then transferred to the antibody-coated wells and incubated for 1 h at room temperature. Assessment of color development is described in Supplementary information. Extinction was measured at 450 nm. The data generated were analysed by the program PRISM. Normalized values were used to calculate the IC50 by a nonlinear regression curve fit (variable slope) [1].
动物实验 Six weeks old female athymic nude mice (nu/nu) weighing about 16-20 gram were housed by Laboratory Animal Services Centre of The Chinese University of Hong Kong. The experiment was conducted by researchers under license from the Hong Kong Government Department of Health and according to approval given by Animal Experimentation Ethics Committee of the Chinese University of Hong Kong. ESCC xenografts were established by inoculating HKESC-2 (0.6 × 10^5 cells re-suspended in 50 μl of HBSS-buffer) subcutaneously into both flanks of the nude mice. When tumor size reached to 4-6 mm diameter, they were randomized in either treatment (15 mg/kg) or vehicle control group. Afatinib for treatment was prepared by dissolving in 0.5% methylcellulose before administration. Either drug or vehicle was administered to mouse by oral gavage in a schedule of 5 days on plus 2 days off for two weeks. Drug efficacy was evaluated by monitoring the change in tumor size with caliper. Tumor volume was calculated with the formula Tumor Volume = (width2 × length)/2 [2].
别名 BIBW2992, 阿法替尼
分子量 485.94
分子式 C24H25ClFN5O3
CAS No. 439081-18-2

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

H2O: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 90 mg/mL (185.2 mM)

Ethanol: 12 mg/mL (24.7 mM)

溶液配制表

可选溶剂 浓度 体积 质量 1 mg 5 mg 10 mg 25 mg
DMSO / Ethanol 1 mM 2.0579 mL 10.2893 mL 20.5787 mL 51.4467 mL
5 mM 0.4116 mL 2.0579 mL 4.1157 mL 10.2893 mL
10 mM 0.2058 mL 1.0289 mL 2.0579 mL 5.1447 mL
20 mM 0.1029 mL 0.5145 mL 1.0289 mL 2.5723 mL
DMSO 50 mM 0.0412 mL 0.2058 mL 0.4116 mL 1.0289 mL
100 mM 0.0206 mL 0.1029 mL 0.2058 mL 0.5145 mL

计算器

摩尔浓度计算器
稀释计算器
配液计算器
分子量计算器
=
X
X
X
=
X
=
/
g/mol

输入分子式,点击计算,可计算出产品的分子量。

参考文献

1. Li D, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008 Aug 7;27(34):4702-11. 2. Wong CH, et al. Preclinical evaluation of afatinib (BIBW2992) in esophageal squamous cell carcinoma (ESCC). Am J Cancer Res. 2015 Nov 15;5(12):3588-99. 4. Lu H H, Lin S Y, Weng R R, et al. Fucosyltransferase 4 shapes oncogenic glycoproteome to drive metastasis of lung adenocarcinoma[J]. EBioMedicine. 2020, 57: 102846 5. Lu H H, Lin S Y, Roc Weng R, et al. Fucosyltransferase 4 shapes oncogenic glycoproteome to drive metastasis of lung adenocarcinoma[J]. EBioMedicine. 2019 6. Luo P, Yan H, Du J, et al. PLK1 (polo like kinase 1)-dependent autophagy facilitates gefitinib-induced hepatotoxicity by degrading COX6A1 (cytochrome c oxidase subunit 6A1)[J]. Autophagy. 2020: 1-17.

文献引用

1. Luo P, Yan H, Du J, et al. PLK1 (polo like kinase 1)-dependent autophagy facilitates gefitinib-induced hepatotoxicity by degrading COX6A1 (cytochrome c oxidase subunit 6A1). Autophagy. 2021 Oct;17(10):3221-3237. 2. Lu H H, Lin S Y, Roc Weng R, et al. Fucosyltransferase 4 shapes oncogenic glycoproteome to drive metastasis of lung adenocarcinoma. EBioMedicine. 2020, 57: 102846 3. Shang J, Ning S, Chen Y, et al. MDL-800, an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer. Acta Pharmacologica Sinica. 2021, 42(1): 120-131
Endoxifen (Z-isomer) PD-118057 AZD-5672 Rilzabrutinib RG14620 BMS-690514 BI-4142 (S)-Sunvozertinib

相关化合物库

该产品包含在如下化合物库中:
酪氨酸激酶分子库 儿童药物库 FDA 上市激酶抑制剂库 自噬库 JAK-STAT 化合物库 人代谢物化合物库 抗结直肠癌化合物库 含氟化合物库 细胞凋亡化合物库 免疫/炎症分子化合物库

剂量换算

对于不同动物的给药剂量换算,您也可以参考 更多...

体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。

体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。

第一步:请输入动物实验的基本信息
剂量
mg/kg
每只动物体重
g
给药体积
μL
动物数量
第二步:请输入动物体内配方组成,不同的产品配方组成不同,如有配方需求,可先联系我们提供正确的体内配方。
% DMSO
%
% Tween 80
% ddH2O
计算 重置

技术支持

您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。

Keywords

(S)-Afatinib 439081-18-2 Angiogenesis JAK/STAT signaling Tyrosine Kinase/Adaptors EGFR HER BIBW 2992 BIBW2992 阿法替尼 Afatinib BIBW-2992 Inhibitor inhibitor inhibit

 

陶术
生物
TargetMol®中国区唯一合作伙伴
点击进入陶术生物官网陶术生物
联系我们
400-820-0310

上海市静安区江场三路238号8楼