Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity.

By C. Yun, T. Boggon, Yiqun Li, M. S. Woo, H. Greulich, Matthew Meyerson, M. Eck. Cancer Cell, 2007

1,098 citations recorded by the source corpus.

Subfields: Molecular Biology, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/509cbbb846825f872e916367b17b329e6ba6a2c5

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

1. Carlos L. Arteaga
2. J. Engelman
3. Ping Wee
4. Matthew Meyerson
5. M. Eck
6. Zhixiang Wang
7. Nathanael S. Gray
8. L. Jones

In Oncology

1. J. Engelman
2. P. Jänne
3. Ping Wee
4. Carlos L. Arteaga
5. Zhixiang Wang
6. Nathanael S. Gray
7. L. Jones

In Pulmonary and Respiratory Medicine

1. J. Engelman
2. Carlos L. Arteaga
3. P. Jänne
4. Jin-Yuan Shih
5. Shang-Gin Wu

Citations in the corpus

• Developing irreversible inhibitors of the protein kinase cysteinome (2013, positive): “This mutation is believed to induce resistance by decreasing the Km for ATP thereby increasing the concentration of inhibitor needed to efficiently inhibit signaling (Yun et al., 2007).”
• Emerging functions of the EGFR in cancer (2017, background): “Published by FEBS Press and John Wiley & Sons Ltd. molecule inhibitors targeting the tyrosine kinase domain.”
• Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment (2009, neutral): “Introduction of the L834R mutation, commonly found in lung cancer patients, increases the activity of the kinase core by $14-fold, consistent with previous results (Yun et al., 2007; Zhang et al., 2006) (Figure 2A).”
• Mechanisms of receptor tyrosine kinase activation in cancer (2018, neutral): “These mutations hyperactivate the kinase and, subsequently, its downstream signaling, conferring oncogenic properties [32, 36, 37].”
• The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP (2008, methodology): “We also examined binding of the pyrrolopyrimidine compound AEE788 (Novartis Pharmaceuticals), which binds in a manner similar to gefitinib despite the difference in chemical scaffold (8).”
• Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways (2017, background): “Termed a “classical” activating mutation, the L858R mutation of the activation loop confers 50-fold more kinase activity and higher KM for ATP than wild type EGFR [83,84].”
• Overcoming EGFR T790M and C797S resistance with mutant-selective allosteric inhibitors (2016, positive): “EGFR kinase proteins were purified by glutathione-affinity chromatography followed by size-exclusion chromatography after cleavage with TEV or thrombin to remove the GST fusion partner following established procedures 14,23 .”