BIBW2992 (Afatinib) is a novel irreversible dual EGFR and HER2 tyrosine kinase inhibitor. The potency of BIBW2992 on the EGFR and HER2 kinases revealed IC50 values of 0.5 nM and 14 nM, respectively. BIBW2992 suppresses transformation in isogenic cell-based assays, inhibits survival of cancer cell lines and induces tumor regression in xenograft and transgenic lung cancer models, with superior activity over erlotinib.
Another CAS# 850140-72-6
J Virol. 2020 Feb 14;94(5):e01791-19.
|Source||Am J Cancer Res (2015). Figure 3. BIBW2992|
|Cell Lines||HKESC-2 and EC-1 cell lines|
|Incubation Time||24 h|
|Results||In HKESC-2 and EC-1 cell lines, afatinib could suppress AKT phosphorylation in a dose and time dependent manner, in which the phosphorylation was almost completely abrogated when the cells were treated with concentrations around their corresponding IC50 (HKESC-2: 0.1 μM, EC-1: 1 μM) for 24 hours (Figure 3).|
|Source||Am J Cancer Res (2015). Figure 1. BIBW2992|
|Cell Lines||ESCC cell lines|
|Incubation Time||48 and 72 h|
|Results||All 5 ESCC cell lines were sensitive to afatinib, in which over 95% of growth inhibition was observed after 48 and 72 hours of treatment (Figure 1B).|
|Cell lines||NSCLC cells H1666, H3255 and NCI-H1975|
|Preparation method||Growth inhibition of lung cancer cell lines by BIBW2992 and other EGFR and/or HER2 inhibitors (a) Sensitivity of NSCLC cell lines that express EGFR WT, Exon 19 Del, L858R/ T790M and HER2 INS776V to BIBW2992 and erlotinib. Dose-dependent growth inhibition was determined by MTS assay. Only HCC827 cells are sensitive to erlotinib whereas NCIH1781 and NCI-H1975 cells are also sensitive to BIBW2992. Points, average of two independent experiments, each done in triplicate; bars, s.d. *A549 cells harbor a Kras G12S mutation. See also in Supplementary Table 4. (b) Inhibition of anchorage independent cell proliferation of various lung cancer cell lines treated with BIBW2992, lapatinib, canertinib, gefitinib or erlotinib. The IC50 values were determined as described.|
|Incubation time||72 h|
|Animal models||A431 cells mouse bearing tumor xenograft model|
|Formulation||0.5% methocellulose-0.4% polysorbate-80 (Tween 80)|
|Dosages||20 ml/kg body weight once daily|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
|Solubility||DMSO ≥ 80 mg/mL|
A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer.
Schuler et al. Breast Cancer Res Treat. 2012 Aug;134(3):1149-59. PMID: 22763464.
A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab.
Lin et al. Breast Cancer Res Treat. 2012 Jun;133(3):1057-65. PMID: 22418700.
Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu.
De Grève et al. Lung Cancer. 2012 Apr;76(1):123-7. PMID: 22325357.
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Tucatinib, also known as Irbinitinib and ONT-380, is an orally bioavailable inhibitor of the human epidermal growth factor receptor tyrosine kinase ErbB-2 (HER2).
Lazertinib, also known as YH-25448 and GNS-1480, is an oral active, highly potent, mutant-selective and irreversible EGFR Tyrosine-kinase inhibitors (TKIs) targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR.
Pyrotinib (SHR-1258) is an orally bioavailable, potent and selective EGFR/HER2 dual inhibitor, with IC50 values of 13 and 38 nM, respectively.
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