Advances in click chemistry for drug discovery and development

Click chemistry, first introduced by Sharpless and colleagues in 2001, has been an essential tool of drug research owing to its modularity, high efficiency, excellent yields, chemoselectivity, and mild reaction conditions.

This review provides an overview of recent advances in drug development based on click chemistry over the past five years. It highlights key applications including fluorescent probes, lead identification and optimization, drug delivery systems, as well as emerging therapeutic modalities such as antibody-drug conjugates and protein degraders. The literature search was primarily conducted using PubMed and Web of Science.

Click chemistry serves as a powerful enabler of accelerated drug discovery and development. Nevertheless, its clinical translation faces challenges such as physiological interference, pharmacokinetic requirements, and the potential toxicity of metal catalysts. Going forward, research should prioritize optimizing click chemistry reactions to enhance biocompatibility, safety, and stability. Meanwhile, combining click chemistry with artificial intelligence offers promise for identifying structurally diverse candidate molecules that are also synthetically feasible.