Rapid synthesis of proteolysis-targeting chimeras by consecutive click assembly

Abstract

An efficient strategy to access proteolysis-targeting chimeras (PROTACs) is disclosed. Consecutive click assembly of readily available functional modules enables the rapid and modular synthesis of PROTACs. In this manuscript, we demonstrate the synthesis of a range of PROTACs from an E3 ligase ligand and an epidermal growth factor receptor (EGFR) ligand, conveniently diversified with functional modules by triple-click assembly, together with the evaluation of their bioactivity.