Advances in Quinazolinone-Based Tumor-Targeted Inhibitors.

Quinazolinone derivatives, characterized by their unique heterocyclic scaffold and extensive structural tunability, hold considerable promise as targeted antitumor agents. This review systematically summarizes recent advances in the antitumor pharmacology, multifaceted mechanisms of action, and target inhibitor development of this compound class. Mechanistically, quinazolinone derivatives exert antitumor effects through multiple pathways, most prominently the potent inhibition of tyrosine kinases (e.g., EGFR and VEGFR), which is supported by extensive preclinical and clinical evidence. Additional mechanisms include downregulation of the PI3K/AKT/mTOR signaling axis, disruption of cell cycle progression, and interference with epigenetic regulatory proteins. These actions collectively lead to the blockade of tumor cell proliferation signals, induction of mitochondrial-dependent apoptosis, and attenuation of tumor angiogenesis and metabolic reprogramming. Structure-activity relationship (SAR) studies show that adding specific substituents boosts both target selectivity and pharmacokinetic properties. Notably, novel derivatives with dual-target synergy inhibit tumor growth and overcome drug resistance, offering new strategies against tumor heterogeneity.