The rapid expansion of click chemistry reflects its transformative influence on contemporary drug discovery. This review highlights major advances in the application of click reactions within the kinetic target-guided synthesis (KTGS) paradigm for identifying potent inhibitors across a broad range of biological targets. KTGS constitutes a methodological shift that leverages the inherent dynamics of biomolecular systems, enabling biological targets to direct the in situ assembly of high-affinity bidentate ligands from a diverse repertoire of reactive building blocks. The review systematically classifies the principal bond-forming reactions that underpin effective inhibitor generation via KTGS. Collectively, it provides a comprehensive and scholarly analysis of how click-chemistry-enabled KTGS is redefining drug discovery and expediting the development of next-generation therapeutics.
Parvatkar et al. (Wed,) studied this question.