title: Monitoring Conformational Changes in the Receptor Tyrosine Kinase EGFR.
abstract: The receptor tyrosine kinase EGFR is regulated by complex conformational changes, and this conformational control is disturbed in certain types of cancer. Many ligands are known to bind EGFR in its active conformation, thereby preventing ATP from binding. Only a few ligands are known to stabilize EGFR in its inactive conformation, thus providing novel strategies for perturbing EGFR activity. We report a direct binding assay that enables the identification of novel ligands that bind to and stabilize the inactive conformation of EGFR.
authors.affiliation: Technische Universität Dortmund, Fakultät für Chemie und Chemische Biologie, Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.affiliation: Chemical Genomics Centre, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 15, 44227, Dortmund, Germany.|University of Cologne, Department of Mathematics and Natural Sciences, Institute of Biochemistry, Otto-Fischer-Strasse 12-14, 50674, Köln, Germany.
authors.forename: Sinan
authors.initials: S
authors.lastname: Öcal
authors.affiliation: Chemical Genomics Centre, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 15, 44227, Dortmund, Germany.|University of Science, Vietnam National University-Ho Chi Minh City, 227 Nguyen Van Cu Str., Dist. 5, Ho Chi Minh City, Vietnam.
authors.forename: Hoang D
authors.initials: HD
authors.lastname: Nguyen
authors.affiliation: Chemical Genomics Centre, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 15, 44227, Dortmund, Germany.|University of Science, Vietnam National University-Ho Chi Minh City, 227 Nguyen Van Cu Str., Dist. 5, Ho Chi Minh City, Vietnam.
authors.forename: Trang
authors.initials: T
authors.lastname: Phan
authors.affiliation: Technische Universität Dortmund, Fakultät für Chemie und Chemische Biologie, Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Keul
authors.affiliation: Chemical Genomics Centre, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 15, 44227, Dortmund, Germany.|Amgen Inc., 360 Binney Street, Cambridge, MA, 02142, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Simard
authors.affiliation: Technische Universität Dortmund, Fakultät für Chemie und Chemische Biologie, Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany. daniel.rauh@tu-dortmund.de.|Chemical Genomics Centre, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 15, 44227, Dortmund, Germany. daniel.rauh@tu-dortmund.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauh
mesh_terms: D001665:Binding Sites; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride / Q000737:chemistry / Q000378:metabolism; D000077341:Lapatinib; D008024:Ligands; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D008024:Ligands; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077341:Lapatinib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: cancer; direct binding assay; fluorescence spectroscopy; inhibitors; receptor tyrosine kinase