Conformational Insight on WT- and Mutated-EGFR Receptor Activation and Inhibition by Epigallocatechin-3-Gallate: Over a Rational Basis for the Design of Selective Non-Small-Cell Lung Anticancer Agents

International Journal of Molecular Sciences
Cristina MinnelliRoberta Galeazzi

Abstract

Non-small cell lung cancer (NSCLC) represents a difficult condition to treat, due to epidermal growth factor receptor (EGFR) kinase domain mutations, which lead to ligand-independent phosphorylation. Deletion of five amino acids (ELREA) in exon 19 and mutational change from leucine to arginine at position 858 (L858R) are responsible for tyrosine kinase domain aberrant activation. These two common types of EGFR-mutated forms are clinically associated with high response with Tyrosine Kinase Inhibitors (TKI); however, the secondary T790M mutation within the Tyrosine Kinase Domain (TKD) determines a resistance to these EGFR-TKIs. Using molecular dynamic simulation (MD), the present study investigated the architectural changes of wild-type and mutants EGFR's kinase domains in order to detect any conformational differences that could be associated with a constitutively activated state and thus to evaluate the differences between the wild-type and its mutated forms. In addition, in order to evaluate to which extent the EGFR mutations affect its inhibition, Epigallocatechin 3-Gallate (EGCG) and Erlotinib (Erl), known EGFR-TKI, were included in our study. Their binding modes with the EGFR-TK domain were elucidated and the binding differ...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Mar 1, 1985·Physical Review A: General Physics·W G Hoover
Jun 25, 1999·Pacific Symposium on Biocomputing·M F SannerA J Olson
Dec 12, 2003·Bioinformatics·András Fiser, Andrej Sali
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
Sep 6, 2005·Cancer Research·Bruce E Johnson, Pasi A Jänne
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Oct 19, 2005·International Journal of Cancer. Journal International Du Cancer·Hisayuki Shigematsu, Adi F Gazdar
Jul 18, 2006·Nucleic Acids Research·Alessio CeroniPaolo Frasconi
Jan 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cai-Hong YunMichael J Eck
Jun 25, 2008·Annual Review of Biophysics·Kathryn M Ferguson
Mar 26, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kwok-K WongHoward A Burris
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Aug 15, 2009·The Oncologist·Nicholas ThatcherUNKNOWN U.K. Erlotinib Skin Toxicity Management Consensus Group
Sep 10, 2009·Clinical and Experimental Immunology·E MartinelliF Ciardiello
Dec 21, 2010·Journal of Translational Medicine·Sara SimonettiRafael Rosell
Nov 22, 2011·Nature Structural & Molecular Biology·Zhihong WangPhilip A Cole
Oct 30, 2012·The Biochemical Journal·Jin H ParkRavi Radhakrishnan
Nov 20, 2013·Annals of Thoracic Medicine·Abdul-Rahman JaziehM Hassan Murad
Jan 31, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H A YuG J Riely
May 23, 2014·Journal of Chemical Information and Modeling·Rashmi KumariAndrew Lynn
Oct 31, 2014·Molecular BioSystems·Gabbianelli RositaGaleazzi Roberta
Dec 31, 2014·Nature Methods·Jianyi YangYang Zhang
Jan 27, 2015·Annual Review of Biochemistry·Erika KovacsJohn Kuriyan
Dec 3, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Natalia SutimanBalram Chowbay
Mar 16, 2017·International Journal of Cancer. Journal International Du Cancer·Zuyao YangJinling Tang
Jul 30, 2017·European Journal of Medicinal Chemistry·Sandra N MilikKhaled A M Abouzid
Sep 4, 2017·Cancer Metastasis Reviews·Mary Jue XuJennifer R Grandis
Sep 25, 2017·Scientific Reports·Ayana Dagan-WienerMasha Y Niv
Nov 11, 2017·Molecular Oncology·Sara SigismundLetizia Lanzetti
Feb 22, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Emiliano LaudadioRoberta Galeazzi
Jun 7, 2018·Biochemistry and Biophysics Reports·Mika K KanekoYukinari Kato
Jul 5, 2018·Organic & Biomolecular Chemistry·Roberta GaleazziTatiana Armeni

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Citations

Nov 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Motofumi KumazoeHirofumi Tachibana
Jan 21, 2021·Antioxidants·Claudia MusialMagdalena Gorska-Ponikowska
May 27, 2021·Pharmacogenomics·Shanshan WuXun Gu

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mmpbsa
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