A comprehensive description of VEGF-R1/2 small molecule inhibitors as anticancer agents

Vascular endothelial growth factor receptor (VEGFR), a key member of the tyrosine kinase receptor family located on the cell membrane, comprises VEGF-R1, VEGFR-2, and VEGF-R3. VEGFR binds to vascular endothelial growth factor (VEGF) and plays an essential role in regulating angiogenesis. Given its critical involvement in tumor progression, targeting VEGFR has become one of the pivotal strategies in anti-tumor therapy. In this review, we systematically summarize, classify, and analyze VEGFR inhibitors reported from the 2020 to 2025, aiming to provide insights into their potential for treating various tumors. These inhibitors can be broadly categorized into four major classes: Imidazole, pyridine, pyrimidine, pyrrole, indole, purine, indazole, quinoline, quinoxaline, and triazole derivatives. This review offers a comprehensive overview of the structural features, structure-activity relationships (SAR), and pharmacological profiles of novel VEGFR inhibitors, which will assist pharmaceutical chemists in the rational design of effective drugs for combating related tumors.