Journal ArticleDOI
Design and synthesis of quinazolinones as EGFR inhibitors to overcome EGFR resistance obstacle
TLDR
New derivatives of 4(3H)-quinazolinones synthesized and evaluated for their inhibitory activity against NSCLC showed that compounds 15, 51, 73, 75, 78, 79 and 96 could be the promising template to overcome drug resistance mediated by the EGFR T790 Mutant.About:
This article is published in Bioorganic & Medicinal Chemistry.The article was published on 2017-05-15. It has received 30 citations till now. The article focuses on the topics: Gefitinib & EGFR inhibitors.read more
Citations
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Synthesis, anticancer activity and molecular modeling studies of 1,2,4-triazole derivatives as EGFR inhibitors.
Hany A.M. El-Sherief,Bahaa G.M. Youssif,Syed Nasir Abbas Bukhari,Ahmed H. Abdelazeem,Mohamed Abdel-Aziz,Hamdy M. Abdel-Rahman +5 more
TL;DR: The results revealed that compound 14d showed promising EGFR inhibitory activity of cancer cell proliferation and were also observed to be moderate BRAF and tubulin inhibitors.
Journal ArticleDOI
Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors.
Harald Engelhardt,Dietrich Böse,Mark Petronczki,Dirk Scharn,Gerd Bader,Anke Baum,Andreas Bergner,Eugene Chong,Sandra Döbel,Georg Egger,Christian Engelhardt,Peter Ettmayer,Julian E. Fuchs,Thomas Gerstberger,Nina C. Gonnella,Andreas Grimm,Elisabeth Grondal,Nizar Haddad,Barbara Hopfgartner,Roland Kousek,Mariusz Krawiec,Monika Kriz,Lyne Lamarre,Joyce C. Leung,Moriz Mayer,Nitinchandra D. Patel,Biljana Peric Simov,Jonathan T. Reeves,Renate Schnitzer,Andreas Schrenk,Bernadette Sharps,Flavio Solca,Heinz Stadtmüller,Zhulin Tan,Tobias Wunberg,Andreas Zoephel,Darryl B. McConnell +36 more
TL;DR: BI-4020 is described, which is a non-covalent, wild-type EGFR sparing, macrocyclic TKI that potently inhibits the above described EGFR variants and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model.
Journal ArticleDOI
Novel quinazoline-based EGFR kinase inhibitors: A review focussing on SAR and molecular docking studies (2015-2019).
Parth Bhatia,Vrinda Sharma,Ozair Alam,Ajay Manaithiya,Perwaiz Alam,Kahksha,Tauquir Alam,Mohd. Imran +7 more
TL;DR: This review has summarized the work done in the last five years to overcome the limitations of currently marketed drugs, giving structural activity relationships of quinazoline-based lead compounds synthesized and tested recently.
Journal ArticleDOI
Design, synthesis and in vitro biological evaluation of quinazolinone derivatives as EGFR inhibitors for antitumor treatment
Yi Le,Yi-Yuan Gan,Yihong Fu,Jiamin Liu,Wen Li,Xue Zou,Zhixu Zhou,Zhenchao Wang,Gui-Ping Ouyang,Longjia Yan +9 more
TL;DR: Molecular docking data indicates that the compound 5k may exert inhibitory activity by forming stable hydrogen bonds with the R817, T830 amino acid residues and cation-Π interaction with the K72 residue of EGFRwt-TK.
Journal Article
HKI-272 in non-small cell lung cancer. Discussion
Kwok-Kin Wong,Thomas R. Lynch,Jeffrey A. Engelman,Roman Perez-Soler,Bruce E. Johnson,Lecia V. Sequist,Mark A. Socinski +6 more
TL;DR: HKI-272 as discussed by the authors is an irreversible EGFR/HER/ErbB inhibitor that has been shown to inhibit the growth of T790M mutant cells in vitro in human lung cancer cell lines and in murine cells transfected with sensitizing EGFR mutations.
References
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Cancer statistics, 2012
TL;DR: The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 1,024,400 deaths from cancer, which can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket.
Journal ArticleDOI
Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy.
Richard A. Friesner,Jay L. Banks,Robert B. Murphy,Thomas A. Halgren,Jasna Klicic,Daniel T. Mainz,Matthew P. Repasky,Eric H. Knoll,Mee Shelley,Jason K. Perry,David E. Shaw,Perry Francis,Peter S Shenkin +12 more
TL;DR: Glide approximates a complete systematic search of the conformational, orientational, and positional space of the docked ligand to find the best docked pose using a model energy function that combines empirical and force-field-based terms.
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Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening.
Thomas A. Halgren,Robert B. Murphy,Richard A. Friesner,Hege S. Beard,Leah L. Frye,W. Thomas Pollard,Jay L. Banks +6 more
TL;DR: Comparisons to results for the thymidine kinase and estrogen receptors published by Rognan and co-workers show that Glide 2.5 performs better than GOLD 1.1, FlexX 1.8, or DOCK 4.01.
Journal ArticleDOI
EGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Susumu Kobayashi,Titus J. Boggon,Tajhal Dayaram,Pasi A. Jänne,Olivier Kocher,Matthew Meyerson,Bruce E. Johnson,Michael J. Eck,Daniel G. Tenen,Balazs Halmos,Balazs Halmos +10 more
TL;DR: In this paper, the authors reported the case of a patient with EGFR-mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a relapse after two years of complete remission.
Journal ArticleDOI
Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain
William Pao,Vincent A. Miller,Katerina Politi,Gregory J. Riely,Romel Somwar,Maureen F. Zakowski,Mark G. Kris,Harold E. Varmus +7 more
TL;DR: Biochemical analyses of transfected cells and growth inhibition studies with lung cancer cell lines demonstrate that the T790M mutation confers resistance to EGFR mutants usually sensitive to either gefitinib or erlotinib, which should help guide the search for more effective therapy against a specific subset of lung cancers.