Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism

Targeting the EGFR with small-molecule inhibitors is a confirmed valid strategy in cancer therapy. Since the FDA approval of the first EGFR-TKI, erlotinib, great efforts have been devoted to the discovery of new potent inhibitors. Until now, fourteen EGFR small-molecule inhibitors have been globally...

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Autores principales:	Mohammed A. S. Abourehab, Alaa M. Alqahtani, Bahaa G. M. Youssif, Ahmed M. Gouda
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	EGFR kinase inhibitor synthesis anticancer metabolism Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/3499b256055c44e789e51efe9a65e191
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spelling	oai:doaj.org-article:3499b256055c44e789e51efe9a65e1912021-11-11T18:38:08ZGlobally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism10.3390/molecules262166771420-3049https://doaj.org/article/3499b256055c44e789e51efe9a65e1912021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6677https://doaj.org/toc/1420-3049Targeting the EGFR with small-molecule inhibitors is a confirmed valid strategy in cancer therapy. Since the FDA approval of the first EGFR-TKI, erlotinib, great efforts have been devoted to the discovery of new potent inhibitors. Until now, fourteen EGFR small-molecule inhibitors have been globally approved for the treatment of different types of cancers. Although these drugs showed high efficacy in cancer therapy, EGFR mutations have emerged as a big challenge for these drugs. In this review, we focus on the EGFR small-molecule inhibitors that have been approved for clinical uses in cancer therapy. These drugs are classified based on their chemical structures, target kinases, and pharmacological uses. The synthetic routes of these drugs are also discussed. The crystal structures of these drugs with their target kinases are also summarized and their bonding modes and interactions are visualized. Based on their binding interactions with the EGFR, these drugs are also classified into reversible and irreversible inhibitors. The cytotoxicity of these drugs against different types of cancer cell lines is also summarized. In addition, the proposed metabolic pathways and metabolites of the fourteen drugs are discussed, with a primary focus on the active and reactive metabolites. Taken together, this review highlights the syntheses, target kinases, crystal structures, binding interactions, cytotoxicity, and metabolism of the fourteen globally approved EGFR inhibitors. These data should greatly help in the design of new EGFR inhibitors.Mohammed A. S. AbourehabAlaa M. AlqahtaniBahaa G. M. YoussifAhmed M. GoudaMDPI AGarticleEGFRkinase inhibitorsynthesisanticancermetabolismOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6677, p 6677 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	EGFR kinase inhibitor synthesis anticancer metabolism Organic chemistry QD241-441
spellingShingle	EGFR kinase inhibitor synthesis anticancer metabolism Organic chemistry QD241-441 Mohammed A. S. Abourehab Alaa M. Alqahtani Bahaa G. M. Youssif Ahmed M. Gouda Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism
description	Targeting the EGFR with small-molecule inhibitors is a confirmed valid strategy in cancer therapy. Since the FDA approval of the first EGFR-TKI, erlotinib, great efforts have been devoted to the discovery of new potent inhibitors. Until now, fourteen EGFR small-molecule inhibitors have been globally approved for the treatment of different types of cancers. Although these drugs showed high efficacy in cancer therapy, EGFR mutations have emerged as a big challenge for these drugs. In this review, we focus on the EGFR small-molecule inhibitors that have been approved for clinical uses in cancer therapy. These drugs are classified based on their chemical structures, target kinases, and pharmacological uses. The synthetic routes of these drugs are also discussed. The crystal structures of these drugs with their target kinases are also summarized and their bonding modes and interactions are visualized. Based on their binding interactions with the EGFR, these drugs are also classified into reversible and irreversible inhibitors. The cytotoxicity of these drugs against different types of cancer cell lines is also summarized. In addition, the proposed metabolic pathways and metabolites of the fourteen drugs are discussed, with a primary focus on the active and reactive metabolites. Taken together, this review highlights the syntheses, target kinases, crystal structures, binding interactions, cytotoxicity, and metabolism of the fourteen globally approved EGFR inhibitors. These data should greatly help in the design of new EGFR inhibitors.
format	article
author	Mohammed A. S. Abourehab Alaa M. Alqahtani Bahaa G. M. Youssif Ahmed M. Gouda
author_facet	Mohammed A. S. Abourehab Alaa M. Alqahtani Bahaa G. M. Youssif Ahmed M. Gouda
author_sort	Mohammed A. S. Abourehab
title	Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism
title_short	Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism
title_full	Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism
title_fullStr	Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism
title_full_unstemmed	Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism
title_sort	globally approved egfr inhibitors: insights into their syntheses, target kinases, biological activities, receptor interactions, and metabolism
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3499b256055c44e789e51efe9a65e191
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Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism

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