Afatinib (BIBW2992) 化学構造
分子量: 485.94




Quality Control & MSDS


  • Compare EGFR Inhibitors
  • 研究分野
  • Combination Therapy
  • Afatinib (BIBW2992)のメカニズム



製品説明 Afatinib (BIBW2992)は不可逆的にEGF受容体/ HER2含むEGF受容体を抑制、 EGFR L858R , EGFR L858R/T790M と HER2を作用すると、 IC50がそれぞれ0.5 nM, 0.4 nM, 10 nM, 14 nMとなる。



EGFR L858R/T790M



0.5 nM

0.4 nM

10 nM

14 nM [1]

In vitro試験 BIBW2992 shows potent activity against both wild-type and mutant forms of EGFR and HER2. It is similar to Gefitinib in potency against L858R EGFR, but about 100-fold more active against the Gefitinib resistant L858R-T790M EGFR double mutant. BIBW2992 exhibits potent effects on both EGFR and HER2 phosphorylation in vivo. It compares favorably to reference compounds (such as Lapatinib et al.) in all cell types tested, such as human epidermoid carcinoma cell line A431 expressing wt EGFR, murine NIH-3T3 cells transfected with wt HER2, as well as breast cancer cell line BT-474 and gastric cancer cell line NCI-N87, which express endogenous HER2. [1]
In vivo試験 Daily oral administration of BIBW2992 at 20 mg/kg for 25 days results in dramatic tumor regression with a cumulative treated/control tumor volume ratio (T/C ratio) of 2%. Reduced phosphorylation of EGFR and AKT is confirmed by immunohistochemical staining of tissue sections. Therefore, like lapatinib and neratinib, BIBW2992 is a next generation tyrosine kinase inhibitor (TKI) that inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases irreversibly. BIBW2992 is not only active against EGFR mutations targeted by first generation TKIs like Erlotinib or Gefitinib, but also against those insensitive to these standard therapies. [1]
臨床試験 A Phase II clinical trial of BIBW2992 for the treatment of cancer has been terminated.

プロトコル (参考用のみ)



In vitro kinase activity assays The wild type tyrosine kinase domain of the human EGFR as well as that of the EGFR L858R/T790M double mutant are fused to Glutathione-S-transferase (GST), and extracted. Enzyme activity is then assayed in the presence of the inhibitor BIBW2992, serially diluted in 50% DMSO. A random polymer pEY (4:1) is used as substrate and biotinylated pEY (bio-pEY) is added as a tracer substrate. The kinase domain of HER2 is cloned using the baculovirus system and extracted similarly to that of EGFR kinase. Details of assays for EGFR, HER2, SRC, BIRK and VEGFR2 kinase activity are available in Supplementary information.



細胞株 NSCLC cells
濃度 0-10 μM
反応時間 1 hour

1 × 104 NSCLC cells are transferred into each well of a 96-well plate and cultured overnight in serum-free media for the EGFR phosphorylation assay. After addition of BIBW2992 on the next day, the plates are incubated at 37 °C for 1 hour. EGF-stimulation is done using 100 ng/mL for 10 min at room temperature. Cells are washed with ice cold PBS, extracted with 120 μL HEPEX buffer per well and shaken at room temperature for 1 hour. In all 2 × 104 cells per well is used for the HER2 phosphorylation assay. Streptavidin precoated plates are coated with anti-EGFR-biotin at 1:100 dilution in blocking buffer and c-erb2/HER2 oncoprotein Ab-5(Clone N24)-Biotin. Cell extracts is then transferred to the antibody-coated wells and incubated at room temperature for 1 hour. Extinction is measured at 450 nm.



動物モデル Athymic NMRI-nu/nu female mice
製剤 In 0.5% methocellulose-0.4% polysorbate-80 (Tween 80)
投薬量 20 mg/kg
投与方法 Oral administration

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)
Body Surface Area (m2)0.0070.0250.
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)



Download Afatinib (BIBW2992) SDF
分子量 485.94


CAS No. 439081-18-2
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 97 mg/mL (199.61 mM)
エタノール 15 mg/mL (30.86 mM)
<1 mg/mL (<1 mM)
In vivo 0.5% methylcellulose/0.2% Tween 80 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 (S,E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide

カスタマーフィードバック (3)

Click to enlarge
Source Int J Proteomics, 2011, 2011, 215496. Afatinib (BIBW2992) purchased from Selleck
Method CEER assay
Cell Lines H460/A549/RFU cell lines
Concentrations 0-10 μM
Incubation Time 4 h
Results This data showed that a potent dose-dependent inhibition of the HER1 and HER2 pathways in the HCC827 cells was observed by treatment with BIBW-2992. Other HER1 and/or HER2 pathway-activated cell lines, H1975 and H1650, were likewise had these pathway activations blocked by the treatment with BIBW-2992.

Click to enlarge
Source Int J Proteomics, 2011, 2011, 215496. Afatinib (BIBW2992) purchased from Selleck
Method Nikon inverted-phase microscope
Cell Lines lung tumor cell lines
Concentrations 0.1/1 µM
Incubation Time two weeks
Results Reduction of cell colony size formation was observed by the treatment with the irreversible HER1/2 inhibitor BIBW-2992 in H1975 and H1650 cells as seen when these cells were grown in an anchorage-dependent manner.

Click to enlarge
Source Dr. Zhang of Tianjin Medical University. Afatinib (BIBW2992) purchased from Selleck
Method Western blot
Cell Lines Breast cancer cells
Concentrations 0-1 nM
Incubation Time 3 h
Results BIBW2992 treatment resulted in a reduction of EGFR phosphorylation in Breast cancer cells.

文献中の引用 (34)



電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)


* 必須

Related EGFR 阻害剤

  • Erlotinib

    Erlotinib is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.

  • Afatinib (BIBW2992) Dimaleate

    Afatinib (BIBW2992) Dimaleate irreversibly inhibits EGFR/HER2 including EGFR(wt), EGFR(L858R), EGFR(L858R/T790M) and HER2 with IC50 of 0.5 nM, 0.4 nM, 10 nM and 14 nM, respectively; 100-fold more active against Gefitinib-resistant L858R-T790M EGFR mutant.

  • Poziotinib (HM781-36B)

    Poziotinib (HM781-36B) is an irreversible pan-HER inhibitor with IC50 of 3.2 nM, 5.3 nM and 23.5 nM for HER1, HER2, and HER4, respectively. Phase 2.

  • AZ5104

    AZ5104, the demethylated metabolite of AZD-9291, is a potent EGFR inhibitor. Phase 1.

  • Gefitinib (ZD1839)

    Gefitinib (ZD1839) は、NR6wtEGFRとNR6W細胞のTyr1173、Tyr992、Tyr1173とTyr992のためのEGFR阻害剤で、IC50 がそれぞれ 37 nM、 37nM、 26 nM 、57 nMです。

    Features:A potent EGFR tyrosine kinase inhibitor.

  • Erlotinib HCl (OSI-744)

    Erlotinib HCl (OSI-744)は、2nMのIC50によるHER1/EGFR阻害剤です。

  • Osimertinib (AZD9291)

    AZD9291 is an oral, irreversible, and mutant-selective EGFR inhibitor with IC50 of 12.92, 11.44 and 493.8 nM for Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR, respectively. Phase 3.

  • Lapatinib

    ラパチニブ(Lapatinib Ditosylateの形で使われる)は、有力なEGFRErbB2 阻害剤で、IC50 がそれぞれ 10.8 と 9.2 nMです。

  • AG-490 (Tyrphostin B42)

    AG-490 (Tyrphostin B42)は、EGFRの選択的な阻害剤、ErbB2とJAK2で、IC50 がそれぞれ 0.1 μM、 13.5 μM、 and ~10 μMです。


Tags: Afatinib (BIBW2992)を買う | Afatinib (BIBW2992)供給者 | Afatinib (BIBW2992)を購入する | Afatinib (BIBW2992)費用 | Afatinib (BIBW2992)生産者 | オーダーAfatinib (BIBW2992) | Afatinib (BIBW2992)代理店
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID