Afatinib dimaleate.|850140-73-7|(双马来酸盐阿法替尼; BIBW 2992MA2)-陌孚医药/Medlife

您当前的位置：

Afatinib dimaleate. (Synonyms: 双马来酸盐阿法替尼; BIBW 2992MA2)

目录号: PC16014 纯度: ≥98%

CAS No. :850140-73-7

商品编号	规格	价格	会员价
PC16014-5mg	5mg	¥401.80	请登录
PC16014-10mg	10mg	¥666.40	请登录
PC16014-50mg	50mg	¥950.60	请登录
PC16014-10mM (in 1mL DMSO)	10mM (in 1mL DMSO)	¥588.00	请登录

Medlife所售产品仅用于科学研究（非临床研究），非药品不可食用，不可用于人体或动物的临床诊断和治疗，我们不为个人提供产品及服务。产品COA等资料，可至下方“质量控制”中下载。

加入购物车在线咨询收藏产品大包装询价

中文名称	Afatinib dimaleate.
中文别名	双马来酸盐阿法替尼;双马来酸阿法替尼;阿法替尼AfatinibBIBW2992;阿法替尼二马来酸盐;阿法替尼双马来酸盐;阿法替尼双马来酸盐仅供科研使用;马来酸阿法替尼;双马来酸阿法替尼（BIBW2992）;2-(二甲基亚膦酰基)苯胺;顺丁烯二酸盐
英文名称	Afatinib dimaleate
英文别名	2-Butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]- 6-quinazolinyl]-4-(dimethylamino)-, (2E)-, (2Z)-2-butenedioate (1:2);Afatinib dimaleate;BIBW2992 DiMaleate;(2E)-N-(4-[(3-chloro-4-fluorophenyl)amino]-7-{[(3S)-tetrahydrofuran-3-yl]oxy}quinazolin- 6-yl)-4-(dimethylamino)but-2-e...;(2E)-N-(4-[(3-chloro-4-fluorophenyl)amino]-7-{[(3S)-tetrahydrofuran-3-yl]oxy}quinazolin- 6-yl)-4-(dimethylamino)but-2-en;(2E)-N-(4-[(3-chloro-4-fluorophenyl)amino]-7-{[(3S)-tetrahydrofuran-3-yl]oxy}quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis[hydrogen (2Z)-but-2-enedioate];(S,E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide maleate;(Z)-but-2-enedioic acid,(E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide;2-Butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]- 6-quinazolinyl]-4-(dimethylamino)-,;2-Butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]- 6-quin...;2-Butenamide,N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-, (2E)-, (2Z)-2-butenedioate (1:2);Afatinib (dimaleate);BIBW2992 Afatinib dimaleate;BIBW2992-MA2;BIBW2992;FR-179643;Afatinib;Afatinib (diMaleate), BIBW2992;Afatinib dimaleate (USAN);Afatinib maleate;Afatinib maleate (JAN);BIBW 2992MA2;BIBW-2992;Gilotrif (TN);BIBW2992-MA2 (Afatinib dimaleate);But-2-enedioic acid;(E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(d
Cas No.	850140-73-7
分子式	C₃₂H₃₃ClFN₅O₁₁
分子量	718.08
包装储存	Sealed and stored at 4℃，, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

生物活性

Afatinib (BIBW 2992) dimaleate is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC₅₀ values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFR, EGFR, EGFR and HER2, respectively. Afatinib dimaleate can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer.

性状

Solid

IC50 & Target[1][2]

EGFR

0.5 nM (IC₅₀)

HER2

14 nM (IC₅₀)

EGFR

0.4 nM (IC₅₀)

EGFR

10 nM (IC₅₀)

体外研究(In Vitro)

Afatinib dimaleate (100 nM) sufficiently prevents heregulin-stimulated HER3 phosphorylation.
Afatinib dimaleate (0-10000 nM) effectively inhibits anchorage-independent proliferation of NIH-3T3 cells ectopically expressing EGFR mutants, and inhibits cell proliferation of H1666, H3255, and NCI 1975 cells.
Afatinib dimaleate (48-72 h)shows growth inhibition in HKESC-1, HKESC-2, SLMT-1 and EC-1 cells.
Afatinib dimaleate (0-1 μM, 24-48 h) inhibits AKT and MAPK pathways, and inhibits EGFR and AKT phosphorylation in ESCC cell lines.
Afatinib dimaleate (0-1 μM, 16-48 h) induces G0/G1 cell cycle arrest in HKESC-2 and EC-1.
Afatinib dimaleate (0-1 μM, 24-48 h) effectively induces apoptotic cell death in HKESC-2 and EC-1.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay

Cell Line:	NIH-3T3 cells, H1666, H3255, and NCI 1975 cells
Concentration:	0, 1, 10, 100, 1000, 10000 nM
Incubation Time:
Result:	Effectively inhibited anchorage-independent proliferation of NIH-3T3 cells ectopically expressing EGFR mutants. Showed inhibition of anchorage independent cell proliferation of various lung cancer cell lines (H1666, H3255, and NCI 1975 cells), with IC₅₀ values of 60 nM, 0.7 nM and 99 nM, respectively.

Cell Viability Assay

Cell Line:	HKESC-1, HKESC-2, SLMT-1 and EC-1 cell lines
Concentration:
Incubation Time:	48 and 72 hours
Result:	Observed over 95% of growth inhibition. The respective IC₅₀ concentrations at 48 hours (HKESC-1=0.078 μM, HKESC-2=0.115 μM, KYSE510=3.182 μM, SLMT-1=4.625 μM and EC-1=1.489 μM) and 72 hours (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) were all in lower micro-molar range.

Western Blot Analysis

Cell Line:	HKESC-2 cells and EC-1 cells
Concentration:	0, 0.01, and 0.1 μM (HKESC-2 cells), 0, 0.1 and 1 μM (EC-1 cells)
Incubation Time:	24 and 48 hours
Result:	Reduced the phosphorylation of EGFR and the endogenous expression level of HER2 receptors in ESCC cells. Suppressed AKT phosphorylation in a dose and time dependent manner. Significantly reduced the phosphorylation level of the downstream effectors of the AKT-mTOR axis especially in HKESC-2 cells. Inhibited the two major downstream pathways of the ErbB/HER axis, namely, AKT and MAPK pathways in ESCC cell lines.

Cell Cycle Analysis

Cell Line:	HKESC-2 cells and EC-1 cells
Concentration:	0, 0.01, and 0.1 μM (HKESC-2 cells), 0, 0.1 and 1 μM (EC-1 cells)
Incubation Time:	16, 24, and 48 hours
Result:	Induced G0/G1 cell cycle arrest in both tested ESCC cell lines in a time and dose dependent manner. In HKESC-2 cells, the percentage of cells in G0/G1 phase was increased from 38.2% to 68.1% at 0.01 μM of afatinib and to 74.7% at 0.1 μM of afatinib, from 24 hours (82.4% G0/G1 arrest at 0.01 μM and 86.2% at 0.1 μM) to 48 hours (from 74.7% to 88.2% for 0.01 μM and 91.0% for 0.1 μM). In EC-1 cells, the percentage of cells arrested in the G0/G1 phase was increased from 59.1% to 66.6% and 72.2% at 24 and 48 hours respectively.

Apoptosis Analysis

Cell Line:	HKESC-2 cells and EC-1 cells
Concentration:	0, 0.01, and 0.1 μM (HKESC-2 cells), 0, 0.1 and 1 μM (EC-1 cells)
Incubation Time:	24 and 48 hours
Result:	Effectively induced cell death by triggering apoptotic mechanisms in ESCC cell lines. Showed a stronger expression level of cleaved Poly (ADP-ribose) polymerase (PARP) in these cell lines.

体内研究(In Vivo)

Afatinib dimaleate (0-20 mg/kg, Orally, daily for 25 days) shows dramatic tumor regression and downregulation of EGFR, HER2, HER3 and AKT phosphorylation.
Afatinib dimaleate (15 mg/kg, Orally, in a schedule of 5 days on plus 2 days off, for two weeks) strongly inhibits the growth of HKESC-2 tumor.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Athymic NMRI-nu/nu female mice (21–31 g, five to six-week-old, transgenic murine lung cancer model and xenograft models)
Dosage:	15 mg/kg, 20 mg/kg
Administration:	Orally, daily for 25 days
Result:	Resulted in dramatic tumor regression with a cumulative treated/control tumor volume ratio (T/C ratio) of 2% in a standard xenograft model of the epidermoid carcinoma cell line A431, and downregulation of EGFR and AKT phosphorylation. Induced regression of large tumors in this HER2-driven model, effectively controlled xenograft tumor formation by the NCIH1975 cell line, expressing EGFR L858R/T790M, with a T/C value of 12% for doses of 20 mg/kg. Induced more than 50% percent tumor reduction after a 4-week treatment period. Downregulated EGFR, HER2 and HER3 phosphorylation.

Animal Model:	Six weeks old female athymic nude mice (nu/nu) (16-20 g)
Dosage:	15 mg/kg
Administration:	Oral gavage in a schedule of 5 days on plus 2 days off, for two weeks
Result:	Strongly inhibited the growth of HKESC-2 tumor. Average tumor sizes of vehicle and treatment at end point are 348 ± 24 mm and 108 ± 36 mm respectively.

运输条件

Room temperature or refrigerated transportation.

储存方式

Sealed and stored at 4℃，, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

ClinicalTrial

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. [Information]

[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 [Information]

[3]. Wang XK, et al. Afatinib circumvents multidrug resistance via dually inhibiting ATP binding cassette subfamily G member 2 体外研究 and in vivo. Oncotarget. 2014 Dec 15;5(23):11971-85. [Information]

[4]. Yoshioka T, et al. Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer. Cancer Sci. 2018 Apr;109(4):1166-1176. [Information]

溶解度数据

体外研究:

H₂O : 50 mg/mL (69.63 mM; Need ultrasonic)

DMSO : ≥ 35 mg/mL (48.74 mM)

* "≥" means soluble, but saturation unknown.

配制储备溶液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	1.3926 mL	6.9630 mL	13.9260 mL
5 mM	0.2785 mL	1.3926 mL	2.7852 mL
10 mM	0.1393 mL	0.6963 mL	1.3926 mL

产品不同，其溶解度不同。建议根据产品选择合适的溶剂配制储备溶液；配成溶液后，建议分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，建议在 6 个月内使用，-20°C 储存时，建议在 1 个月内使用。

体内研究:

建议根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都建议先按照 体外研究 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

建议依照次序添加每种溶剂： PBS
Solubility: 100 mg/mL (139.26 mM); Clear solution; Need ultrasonic

搜索质检报告(COA)

产品使用指南

Data Sheet

1：一般建议：溶解度为Medlife测试数据，可能与文献描述存在差异。这是由于生产工艺和批次不同产生的正常现象。为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。不同批次产品溶解度各有差异，仅做参考，具体以实验方案为准。

2：储存条件：粉末-20°C一般情况可以保存3年，溶于溶剂-80°C一般情况可以保存1年。不同产品及不同批次产品可能存在差异，请细致阅读产品信息，并辅助参考相关文献描述。

相关产品

The molarity calculator equation

The dilution calculator equation