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Recent advances in clinically approved nitrogenous heterocycle-based drugs and EGFR Tyrosine kinase inhibitors for precision oncology (2020–2024): a review
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Recent advances in clinically approved nitrogenous heterocycle-based drugs and EGFR Tyrosine kinase inhibitors for precision oncology (2020–2024): a review
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Recent advances in clinically approved nitrogenous heterocycle-based drugs and EGFR Tyrosine kinase inhibitors for precision oncology (2020–2024): a review
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Journal Article
Recent advances in clinically approved nitrogenous heterocycle-based drugs and EGFR Tyrosine kinase inhibitors for precision oncology (2020–2024): a review
2025
Overview
Cancer is the most lethal disease and one of the most significant and major healthcare challenges worldwide. Although several anticancer drugs are available, many lack specificity, exhibit severe side effects, or develop resistance over time. Protein kinases play a crucial role in biological functions, inducing cell differentiation, survival, modifying cell cycles, and their inhibition activity is connected to tumor growth pathways. The development of drugs that target molecular tyrosine kinase (TK) pathways, such as epidermal growth factor receptor (EGFR), has therefore become a central strategy in precision oncology. EGFR is a key regulator of cellular signaling pathways involved in pathological processes, including apoptosis, uncontrolled cell proliferation, and metastasis. However, clinically used EGFR inhibitors such as lapatinib, gefitinib, vandetanib, and erlotinib are not selective, leading to adverse effects and resistance. These limitations highlight the urgent need for safer, more selective, and effective EGFR inhibitors. More than 85% of all physiologically active pharmaceuticals (clinically approved) contain heterocyclic frameworks, with nitrogenous heterocycles playing a dominant role in drug discovery. This review compiled recent advances (2020–2024) in clinically approved and investigational nitrogenous heterocyclic compounds with EGFR inhibitory therapeutic efficacy. A wide range of nitrogenous heterocycles from four- to seven-membered rings, along with patents, including β-lactam, pyridine, imidazole, quinolone, benzimidazole, quinoxaline, indole, quinazoline, pyrazole, pyrimidine, carbazole, triazole, isatin, and tetrazole derivatives, are discussed as EGFR tyrosine kinase inhibitors (TKIs). Natural nitrogenous heterocycles exhibiting EGFR inhibition is also highlighted. Furthermore, structure–activity relationships (SAR) analyses and pharmacological data are also compiled and summarized to guide the rational design of next-generation EGFR inhibitors. Overall, the plethora of research in this review article provides comprehensive insights into the role of nitrogenous heterocycles as promising scaffolds for precision oncology.
