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Review
. 2023 Jan 31;24(3):2651.
doi: 10.3390/ijms24032651.

Small Molecule EGFR Inhibitors as Anti-Cancer Agents: Discovery, Mechanisms of Action, and Opportunities

Tanzida Zubair  1 , Debasish Bandyopadhyay  1   2
Affiliations
Review

Small Molecule EGFR Inhibitors as Anti-Cancer Agents: Discovery, Mechanisms of Action, and Opportunities

Tanzida Zubair et al. Int J Mol Sci. .

Abstract

Epidermal growth factor receptors (EGFRs) are a class of receptor tyrosine kinase that are also called ErbB1 and HER1. EGFR tyrosine kinase activity inhibition is considered a promising therapeutic strategy for the treatment of cancer. Many small-molecule inhibitors of EGFR tyrosine kinase (EGFR-TK), from medicinally privileged molecules to commercial drugs, have been overviewed. Particular attention has been paid to the structure of the molecule and its mechanism of action if reported. Subsequent classification of the molecules under discussion has been carried out. Both natural and synthetic and reversible and irreversible EGFR-tyrosine kinase inhibitors have been discussed. Various types of cancers that are caused by overexpression of the EGFR gene, their possible molecular origins, and their natures have also been counted in this article. Because the EGFR signaling pathway controls the proliferation, growth, survival, and differentiation of cells, and the mutated EGFR gene overproduces EGFR protein, which ultimately causes several types of cancer, proper understanding of the molecular dynamics between the protein structure and its inhibitors will lead to more effective and selective EGFR-TKIs, which in turn will be able to save more lives in the battle against cancer.

Keywords: anticancer drugs; cancer therapeutics; epidermal growth factor receptor (EGFR); heterocycles; natural cancer drugs; polycyclic compounds; small molecule inhibitors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
First-generation and second-generation small molecule EGFR-TKIs.
Figure 2
Figure 2
Third-generation and Fourth-generation small molecule EGFR-TKIs.
Figure 3
Figure 3
Small molecule natural compounds as EGFR inhibitors.
Figure 4
Figure 4
Co-crystallized structure of EGFR T790M with a pyrimidine derivative WZ4002 (PDB ID: 3IKA) (Image courtesy of RSCB PDB: https://www.rcsb.org, accessed on 31 December 2022) [64].
See this image and copyright information in PMC

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This research received no external funding.