Anti-EGFR Agents: Current Status, Forecasts and Future Directions

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.

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“…It was approved in China in 2018 for use in the treatment of solid tumors. It is indicated for metastatic NSCLC[145].…”

mentioning

confidence: 99%

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

et al. 2021

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“…EGFR is an important and attractive target for specific anticancer therapies [41], and a robust regulator of pathways involved in cancer pathogenesis and progression [41].…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of the potential off-target activities of osimertinib by computational target fishing

Chen

Zhang

2021

Anti-Cancer Drugs

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Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used to treat non-small cell lung cancer. However, its off-targets are obscure, and systematic analysis of off-target activities remains to be performed. Here, we identified the offtargets of osimertinib using PharmMapper and DRAR-CPI and analyzed the intersected targets using the GeneMANIA and DAVID servers. A drug-target-pathway network was constructed to visualize the associations. The results showed that osimertinib is associated with 31 off-targets, 40 Kyoto Encyclopedia of Genes and Genomes pathways, and 9 diseases. Network analysis revealed that the targets were involved in cancer and other physiological processes. In addition to EGFR, molecular docking analysis showed that seven proteins, namely Janus kinase 3, peroxisome proliferator-activated receptor alpha, renin, mitogen-activated protein kinases, lymphocyte-specific protein tyrosine kinase, cell division protein kinase 2 and proto-oncogene tyrosine-protein kinase Src, could also be potential targets of osimertinib. In conclusion, osimertinib is predicted to target multiple proteins and pathways, resulting in the formation of an action network via which it exerts systematic pharmacological effects. Anti-Cancer Drugs 33: e434-e443

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“…Similar to VEGF, epidermal growth factor receptor (EGFR) is a member of the epidermal growth factor receptor (HER) family. As a tyrosine kinase receptor, EGFR is overexpressed in many tumor cells and is a potential biomarker for the recognition of cancer cells [38][39][40]. Piletsky and co-workers prepared molecularly imprinted nanoparticles (nanoMIP) using a doubleimprinting method (Figure 1) [41].…”

Section: Peptidementioning

confidence: 99%

Selective recognition of tumor cells by molecularly imprinted polymers

Gao

et al. 2021

J of Separation Science

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Molecularly imprinted polymers, developed 50 years ago, have garnered enormous attention as receptor-like materials. Lately, molecularly imprinted polymers have been employed as a specific target tool in favor of cancer diagnosis and therapy by the selective recognition of tumor cells. Although the molecular imprinting technology has been well-innovated recently, the cell still remains the most challenging target for imprinting. In this review, we summarize the advances in the synthesis of molecularly imprinted polymers suitable for the selective recognition of tumor cells. Through a sustained effort, three strategies have been developed including peptide-imprinting, polysaccharide-imprinting, and whole-cell imprinting, which have resulted in inspiring applications in effective cancer diagnosis and therapy. The major challenges and perspectives on the further directions related to the synthesis of molecularly imprinted polymers were also outlined.

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Anti-EGFR Agents: Current Status, Forecasts and Future Directions

Cited by 12 publications

References 72 publications

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

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

Systematic analysis of the potential off-target activities of osimertinib by computational target fishing

Selective recognition of tumor cells by molecularly imprinted polymers

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