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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Journal ArticleDOI
Acquired resistance to third-generation EGFR-TKIs and emerging next-generation EGFR inhibitors.
TL;DR: The molecular mechanisms underlying resistance to third-generation EGFR inhibitors and the ongoing efforts to address and overcome this chemoresistance are summarized.
Journal ArticleDOI
A sulfonyl fluoride derivative inhibits EGFRL858R/T790M/C797S by covalent modification of the catalytic lysine.
Francesca Ferlenghi,Laura Scalvini,Federica Vacondio,Riccardo Castelli,Nicole Bozza,Giuseppe Marseglia,Silvia Rivara,Alessio Lodola,Silvia La Monica,Roberta Minari,Pier Giorgio Petronini,Roberta Alfieri,Marcello Tiseo,Marco Mor +13 more
TL;DR: UPR1444 (compound 11) is a new sulfonyl fluoride derivative which potently and irreversibly inhibits EGFRL858R/T790M/C797S through the formation of a sulfonamide bond with the catalytic residue Lys745.
Journal ArticleDOI
Conformational Constrained 4-(1-Sulfonyl-3-indol)yl-2-phenylaminopyrimidine Derivatives as New Fourth-Generation Epidermal Growth Factor Receptor Inhibitors Targeting T790M/C797S Mutations.
Hao Chen,Mengzhen Lai,Tao Zhang,Yuqing Chen,Linjiang Tong,Sujie Zhu,Yang Zhou,Xiaomei Ren,Jianping Ding,Hua Xie,Xiaoyun Lu,Ke Ding +11 more
TL;DR: The structure-based design of conformational constrained 4-(1-ethylsufonyl-3-indolyl)-2-phenylaminopyrimidines as new EGFRT790M/C797S inhibitors are reported by using a macrocyclization strategy to combat EGFRC797S-mediated resistance in NSCLC patients.
Journal ArticleDOI
Design, Synthesis, and Biological Evaluation of Novel EGFR PROTACs Targeting Del19/T790M/C797S Mutation.
TL;DR: The design and synthesis of a series of EGFR proteolysis-targeting chimeras (PROTACs) that can rapidly and potently induce EGFR degradation in Ba/F3 cells expressing the EGFRDel19/T790M/C797S mutant are presented.
Journal ArticleDOI
Recent advances in the development of EGFR degraders: PROTACs and LYTACs.
TL;DR: In this paper , the structural properties of EGFR, the inhibitors that have been developed against WT/mutated EGFR and then mainly focuses on the recent advances of EGfr-targeting degraders along with its limitations and unlimited prospects.
References
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Journal ArticleDOI
Recent Progress of Small-Molecule Epidermal Growth Factor Receptor (EGFR) Inhibitors against C797S Resistance in Non-Small-Cell Lung Cancer
TL;DR: This Miniperspective analyses the allosteric and ATP-competitive inhibitors in terms of drug discovery, binding mechanism, and their potency and selectivity against EGFR harboring C797S mutations and provides some perspectives on new challenges and future directions in this field.
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Design, Synthesis, and Biological Evaluation of Novel Conformationally Constrained Inhibitors Targeting Epidermal Growth Factor Receptor Threonine790 → Methionine790 Mutant
Chang Shaohua,Lianwen Zhang,Lianwen Zhang,Shilin Xu,Jinfeng Luo,Xiaoyun Lu,Zhang Zhang,Tianfeng Xu,Yingxue Liu,Zhengchao Tu,Yong Xu,Xiaomei Ren,Meiyu Geng,Jian Ding,Duanqing Pei,Ke Ding +15 more
TL;DR: A series of 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidinyl derivatives as novel EGFR inhibitors inhibited the enzymatic activities of wild-type and mutated EGFRs and displayed promising anticancer efficacy in a human NSCLC (H1975) xenograft nude mouse model.
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Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer.
TL;DR: Outcomes for metastatic colorectal cancer patients have been improved by treatment with anti-epidermal growth factor receptor (anti-EGFR) antibodies, particularly when combined with predictive biomarkers to select patients lacking RAS mutations.
Journal ArticleDOI
Non-invasive approaches to monitor EGFR-TKI treatment in non-small-cell lung cancer.
TL;DR: Non-invasive techniques based on serum or plasma samples had a great potential for monitoring EGFR-TKI treatment in NSCLC, and a commercialized serum-based proteomic test, named VeriStrat test, has shown an outstanding ability to predict the clinical outcome ofNSCLC patients receiving EGFR
Journal ArticleDOI
Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site
Marcel Günther,Jonas Lategahn,Michael Juchum,Eva Döring,Marina Keul,Julian Engel,Hannah L. Tumbrink,Daniel Rauh,Stefan Laufer +8 more
TL;DR: A rational approach based on extending the inhibition profile of a p38 MAP kinase inhibitor toward mutant EGFR inhibition is presented, and metabolically stable inhibitors with high activities are developed against the osimertinib resistant L858R/T790M/C797S mutant.