Unveiling the power of quinazoline derivatives: a new frontier in targeted cancer therapy

Quinazoline-based scaffolds represent a class of nitrogen-containing heterocycles distinguished by their structural versatility and broad-spectrum anticancer activities, positioning them as key elements in targeted cancer therapy. This review highlights the role of quinazoline derivatives as potent small-molecule inhibitors targeting diverse oncogenic drivers. They effectively modulate critical receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and cellular-mesenchymal epithelial transition factor (c-Met); non-receptor serine/threonine kinases including cyclin-dependent kinases (CDKs), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), Aurora kinases, and hematopoietic progenitor kinase 1 (HPK1); as well as epigenetic, cytoskeletal, and DNA-interacting proteins. Recent advances in structure-activity relationship (SAR) studies, binding analyses, and preclinical evaluations have facilitated scaffold optimization to counter resistance mutations and improve pharmacokinetic properties. Collectively, clinical and experimental evidence underscores quinazoline derivatives as a robust platform for developing next-generation targeted anticancer agents.