Small-molecule compounds exhibit distinct pharmacological properties and clinical effectiveness. Over the past decade, advances in covalent drug discovery have led to successful small-molecule drugs, such as EGFR, BTK, and KRAS (G12C) inhibitors, for cancer therapy. Researchers are paying more attention to refining drug screening methods aiming for high throughput, fast speed, high specificity, and accuracy. Therefore, the discovery and development of small-molecule drugs has been facilitated by significantly reducing screening time and financial resources, and increasing promising lead compounds compared with traditional methods. This review aims to introduce classical and emerging methods for screening small-molecule compounds in targeted cancer therapy. It includes classification, principles, advantages, disadvantages, and successful applications, serving as valuable references for subsequent researchers.
Keywords: Drug screening; computer-aided drug discovery; phenotype-based drug screening; small-molecule compounds; target-based drug screening; targeted cancer therapy.
Classical and emerging methods for screening small-molecule compounds.Target-based drug screening approaches widely used for drug development.Phenotype-based screening approaches for discovering candidate compounds.Chemoproteomics as an unbiased screening technology to identify compound targets.Computer-aided drug discovery to reduce the number of compounds screened experimentally.