Journal ArticleDOI
The new opportunities in medicinal chemistry of fourth-generation EGFR inhibitors to overcome C797S mutation
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TLDR
The recent advances in medicinal chemistry of fourth-generation EGFR-TKIs are discussed, as well as further discussed the clinical challenges and future prospects of treating patients with EGFR mutations resistant to third-generationEGFR- TKIs.About:
This article is published in European Journal of Medicinal Chemistry.The article was published on 2021-01-15. It has received 34 citations till now. The article focuses on the topics: EGFR inhibitors & Epidermal growth factor receptor.read more
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Development of 5-Trifluoromethylpyrimidine Derivatives as Dual Inhibitors of EGFR and SRC for Cancer Therapy
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Design, synthesis and biological evaluation of novel osimertinib derivatives as reversible EGFR kinase inhibitors.
Shi Ding,Ziye Gao,Ziqiang Hu,Rui Qi,Xiangshang Zheng,Xiao-huan Dong,Jinghui Zhang,Jiwei Shen,Tian Long,Yan Zhu,Lu Tian,W. Q. Song,Ruoqing Liu,Ying Li,Jiahuan Sun,Wenwen Duan,Ju Zheng Liu,Ye Chen +17 more
TL;DR: In this paper , a series of osimertinib derivatives without acrylamide groups were synthesized and their inhibitory rates against L858R/T790M/C797S mutated EGFR kinase and antiproliferation activities against non-small cell lung cancer cell lines (A549, H1975) were evaluated.
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Recent Advances in Boosting EGFR Tyrosine Kinase Inhibitors-Based Cancer Therapy.
TL;DR: In this article , the authors summarized the recent progress of oral, pulmonary, and injectable drug delivery systems for enhanced and targeting TKI delivery to tumors and reduced side effects, and provided a perspective on the future research of EGFR-TKI-based cancer therapy.
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Non-small-cell lung cancer: how to manage EGFR-mutated disease
TL;DR: In this article , the authors provide an updated and comprehensive summary of the latest advancements in the quest for compounds targeting EGFR-mutant advanced non-small-cell lung cancer, discussing the biological rationale underlying the development of a forefront combination of TKI and/or new antibody-drug conjugates.
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Mechanistic Modeling of Lys745 Sulfonylation in EGFR C797S Reveals Chemical Determinants for Inhibitor Activity and Discriminates Reversible from Irreversible Agents
Kemel Arafet,Laura Scalvini,Francesca Galvani,Sergio Martí,Vicent Moliner,Marco Mor,Alessio Lodola +6 more
TL;DR: In this article , the authors describe the mechanism of inhibition of an innovative class of compounds that covalently engage the catalytic lysine of EGFR, through a sulfur(VI) fluoride exchange (SuFEx) process, with the help of hybrid quantum mechanics/molecular mechanics (QM/MM) and path collective variables (PCVs) approaches.
References
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Cancer statistics, 2017
TL;DR: The American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival.
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Non-small cell lung cancer, version 5.2017: Clinical practice guidelines in oncology
David S. Ettinger,Douglas E. Wood,Dara L. Aisner,Wallace Akerley,Jessica Bauman,Lucian R. Chirieac,Thomas A. D'Amico,Malcolm M. DeCamp,Thomas J. Dilling,Michael C. Dobelbower,Robert C. Doebele,Ramaswamy Govindan,Matthew A. Gubens,Mark Hennon,Leora Horn,Ritsuko Komaki,Rudy P. Lackner,Michael Lanuti,Ticiana A. Leal,Leah J. Leisch,Rogerio Lilenbaum,Jules Lin,Billy W. Loo,Renato Martins,Gregory A. Otterson,Karen L. Reckamp,Gregory J. Riely,Steven E. Schild,Theresa A. Shapiro,James P. Stevenson,Scott J. Swanson,Kurt Tauer,Stephen C. Yang,Kristina M. Gregory,Miranda Hughes +34 more
TL;DR: This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastasis disease.
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Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors
Yong Jia,Cai-Hong Yun,Eun Young Park,Dalia Ercan,Mari Manuia,Jose Juarez,Chunxiao Xu,Kevin Rhee,Ting Chen,Haikuo Zhang,Sangeetha Palakurthi,Jaebong Jang,Gerald Lelais,Michael DiDonato,Badry Bursulaya,Pierre-Yves Michellys,Robert Epple,Thomas H. Marsilje,Matthew McNeill,Wenshuo Lu,Jennifer L. Harris,Bender Steven Lee,Kwok-Kin Wong,Pasi A. Jänne,Michael J. Eck +24 more
TL;DR: Rational discovery of EAI045 is described, an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild type receptor and shows dramatic synergy of cetuximab, an antibody therapeutic that blocks EGFR dimerization, rendering the kinase uniformly susceptible to theAllosteric agent.
Journal ArticleDOI
The allelic context of the C797S mutation acquired upon treatment with third generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies
Matthew J. Niederst,Haichuan Hu,Hillary E. Mulvey,Elizabeth L. Lockerman,Angel R. Garcia,Zofia Piotrowska,Lecia V. Sequist,Jeffrey A. Engelman +7 more
TL;DR: The results demonstrate that the allelic context in which C797S was acquired may predict responsiveness to alternative treatments, and are a novel mechanism of acquired resistance to third-generation TKIs.
Journal ArticleDOI
Investigating Novel Resistance Mechanisms to Third-Generation EGFR Tyrosine Kinase Inhibitor Osimertinib in Non–Small Cell Lung Cancer Patients
Zhe Yang,Nong Yang,Qiuxiang Ou,Yi Xiang,Tao Jiang,Xue Wu,Hua Bao,Xiaoling Tong,Xiaonan Wang,Yang W. Shao,Yunpeng Liu,Yan Wang,Caicun Zhou +12 more
TL;DR: Novel secondary mutations of EGFR L718 and L792 residues confer osimertinib resistance, both in vitro and in vivo, and are of great clinical and pharmaceutical relevance.