<span lang="EN-GB">Structure-Activity Relationship and Docking Study of Non-Quinazoline EGFR/VEGFR Dual Inhibitors. A Review

The dual inhibitors of Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor ۲ (VEGFR-۲) have been developed as a promising strategy for cancer therapy. These inhibitors are generally classified into two primary categories: quinazoline-based inhibitors and non-quinazoline-based inhibitors, depending on their structural framework. To achieve dual inhibition of these receptor tyrosine kinases, researchers have explored a range of molecular scaffolds. Investigated scaffolds include quinazoline, quinoline, pyrimidine, triazole, benzimidazole, pyrazole, coumarin, thioimidazoline, phthalazine, oxindole, steroid, and chromene structures. While existing reviews largely focus on the attributes of quinazoline-based inhibitors, this review seeks to compile and summarize the Structure-Activity Relationships (SAR), tyrosine kinase inhibitory potential, antiproliferative properties, and docking studies of non-quinazoline EGFR/VEGFR-۲ dual inhibitors. These derivatives offer several advantages, including reduced off-target toxicity, improved ability to overcome resistance mutations, enhanced pharmacokinetic properties, and avoidance of quinazoline-related safety concerns such as cardiac QT risk. The insights discussed in this review are intended to facilitate the development of novel EGFR/VEGFR-۲ dual inhibitors for therapeutic use and to serve as a valuable reference for medicinal chemists in designing next-generation EGFR/VEGFR-۲ tyrosine kinase inhibitors as anticancer agents.

کلیدواژه ها:

Non-quinazolines ، EGFR ، VEGFR-۲ ، Dual inhibitors ، Tyrosine Kinase ، SAR ، Docking