Epidermal growth factor receptor inhibitors as potential anticancer agents: An update of recent progress

• Published in: Bioorganic chemistry Vol. 116; p. 105393
• Main Authors: Sharma, Bharti, Singh, Vikram Jeet, Chawla, Pooja A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2021
• Subjects: Anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Proliferation - drug effects; Cytotoxicity; Drug Screening Assays, Antitumor; EGFR inhibitors; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - metabolism; Heterocyclic compounds; Humans; Molecular Structure; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; SAR; EGFR TKIs; H1975; HL7702; COS-7; SAR; DU-145, PC-3; Cytotoxicity; A549, H460, NCI-H157; WI-28; MTT; EGFR; SMMC-7721; HeLa; Heterocyclic compounds; HepG2; mTOR; VEGFR; HCvEpC; WI38; MCF-10A; NSCLC; EGF; HCT-116, HT-29; PBMCs; A375; SGC; A431; MCF-7, MDA-231, MDA-MB-231, T47D; HER; Raf; GAP; EGFR inhibitors; Anticancer; CCRF-CEM, MOLT-4; HaCaT
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105393

[Display omitted] •EGFR represents important drug targets for the treatment of different cancer.•Recent development in the medicinal chemistry of heterocyclic based EGFR inhibitors.•SAR have been described.•In vitro and in vivo biological activities of numerous EGFR inhibitors.•Mechanism of action and in silico studies are discussed.•The article aids in the rational design and development of novel potent and specific inhibitors. Epidermal growth factor receptor (EGFR) is a vital intermediate in cell signaling pathway including cell proliferation, angiogenesis, apoptosis, and metastatic spread and also having four divergent members with similar structural features, such as EGFR (HER1/ErbB1), ErbB2 (HER2/neu), ErbB3 (HER3), and ErbB4 (HER4). Despite this, clinically exploited inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc.) are not specific thus provoking unenviable adverse effects. Some of the paramount obstacles to generate and develop new lead molecules of EGFR inhibitors are drug resistance, mutation, and also selectivity which inspire medicinal chemists to generate novel chemotypes. The discovery of therapeutic agents that inhibit the precise stage in tumorous cells such as EGFR is one of the chief successful targets in many cancer therapies, including lung and breast cancers. This review aims to compile the various recent progressions (2016–2021) in the discovery and development of diverse epidermal growth factor receptor (EGFR) inhibitors belonging to distinct structural classes like pyrazoline, pyrazole, imidazole, pyrimidine, coumarin, benzothiazole, etc. We have summarized preclinical and clinical data, structure–activity relationships (SAR) containing mechanistic and in silico studies to provide proposals for the design and invention of new EGFR inhibitors with therapeutic significance. The detailed progress of the work in the field will provide inexorable scope for the development of novel drug candidates with greater selectivity and efficacy.