A Unique Structure for Epidermal Growth Factor Receptor Bound to GW572016 (Lapatinib)

By E. Wood, A. Truesdale, O. McDonald, D. Yuan, A. Hassell, S. Dickerson, B. Ellis, C. Pennisi, E. Horne, K. Lackey and 4 more. Cancer Research, 2004

1,075 citations recorded by the source corpus.

Subfields: Oncology

View Paper: https://www.semanticscholar.org/paper/210d143a1318be20027a13ce79d11e6a62e79b2b

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In Oncology

1. William Pao
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4. Vincent A. Miller
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Citations in the corpus

• Mechanisms of Disease: understanding resistance to HER2-targeted therapy in human breast cancer (2006, background): “Third, differences in enzyme-inhibitor structures could account for differences in dissociation off-rate, since EGFR is in a closed conformation when it binds lapatinib and a more open conformation when it binds gefitinib”
• Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. (2007, methodology): “The bulky 4anilino substituent in lapatinib cannot be accommodated in the active conformation of the kinase, and thus lapatinib appears to trap the kinase in the inactive conformation with the C helix displaced (Wood et al., 2004).”
• An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. (2006, background): “Crystal Structure of the V924R Mutant of the EGFR Kinase Domain Reveals a Src/CDK-like Inactive Conformation The Src/CDK-like inactive conformation of the EGFR kinase domain has only been observed in a complex with the drug Lapatinib (Wood et al., 2004), leaving open the possibility that this partic”
• Rational design of inhibitors that bind to inactive kinase conformations (2006, background): “Slow dissociation rates are often linked with protein conformational changes upon ligand binding, as seen in the epidermal growth factor receptor (EGFR) kinase inhibitor lapatini”
• The epidermal growth factor receptor family: Biology driving targeted therapeutics (2008, background): “K and Lonardo, F. (2007) Breast cancer expressing the activated HER2/neu is sensitive to gefitinib in vitro and in vivo and acquires resistance through a novel point mutation in the HER2/neu.”
• Overcoming EGFR T790M and C797S resistance with mutant-selective allosteric inhibitors (2016, neutral): “Interestingly, EGFR inhibitors neratinib 20 and lapatinib 21 extend into the allosteric site and make interactions that resemble those of two of the three blades of the allosteric agents (Fig.”
• Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. (2006, background): “Lapatinib is a reversible inhibitor with estimated dissociation constant (K i) values of 3 and 13 nmol/L for EGFR and HER-2, respectively (23).”
• Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain (2005, background): “For example, the crystal structure of another EGFR inhibitor, lapatinib (GW572016), was recently solved bound to EGFR [26].”
• Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. (2013, background): “Similar lag phases in recovery of intracellular protein phosphorylation have been observed with kinase inhibitors of long residence time.(44) These results suggest that reduced global H3K79 methylation can be used as a pharmacodynamic readout for DOT1L inhibitor activity in vivo, but that there is l”
• Target Binding Properties and Cellular Activity of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker (2012, background): “This binding mode contrasts with the one of lapatinib, which reportedly requires the inactive conformation to accommodate the larger aromatic group attached to the aniline (Wood et al., 2004).”