BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

By Daizong Li, L. Ambrogio, T. Shimamura, S. Kubo, Masaya Takahashi, L. Chirieac, R. Padera, G. Shapiro, A. Baum, F. Himmelsbach and 5 more. Oncogene, 2008

1,413 citations recorded by the source corpus.

Subfields: Molecular Biology, Organic Chemistry, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/742f416ee35c1e065c461c727cce78b79ff0caa7

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Organic Chemistry

L. Jones

In Pulmonary and Respiratory Medicine

Citations in the corpus

Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer (2018, neutral): “fects (AEs), probably owing to inhibition of wild-type EGFR [12, 13].”
Target Binding Properties and Cellular Activity of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker (2012, methodology): “…Type Culture Collection) were grown in RPMI 1640 medium supplemented with 10% fetal calf at A SPE T Journals on D ecem ber 19, 2018 jpet.aspetjournals.org D ow nloaded from serum and prepared for three-dimensional assays (0.3% sea plaque agarose top layer) as described previously (Li et al., 2008).”
Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors (2009, neutral): “In patients with resistance to first-generation EGFR TKIs generated by MET amplification, it is unlikely that an irreversible EGFR inhibitor alone would be effective, but the combination of an irreversible EGFR inhibitor and an mTOR inhibitor may be an effective strategy for overcoming resistance (L”
HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. (2012, background): “Achievable afatinib serum levels at this dose range from 80-667 nM (9); the standard dose in humans is 40 mg po qd; at 45mg, the Cmax is 141 nM (32).”
Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer (2010, background): “gov/drugdictionary/?CdrID=537572">BIBW2992 (afatinib; Boehringer Ingelheim) has potent activity against EGFR and ERBB2 and can overcome T790M-mediated resistance in vitro and in viv o”
Targeting the PI5P4K lipid kinase family in cancer using covalent inhibitors (2020, background): “, 2004), afatinib (Li et al., 2008), and osimertinib (Cross et al.”
Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. (2013, background): “In vitro, the median inhibitory concentration is lower than those of currently available EGFR TKIs.(10) In a large phase II study of EGFR-mutant NSCLC, the response rate to afatinib was 61%(independentreview),withmedianPFSof12monthsfortreatmentnaive patients and 8 months for EGFR TKI–naive patients ”
Developing irreversible inhibitors of the protein kinase cysteinome (2013, positive): “Replacement of one of the quinazoline nitrogens with a nitrile resulted in another set of compounds that advanced to clinical trials: EKB569 (phase II trial completed), HKI-272 (phase III trial), and BIBW-2992 (phase III trial) (Li et al., 2008; Yoshimura et al., 2006).”