Application of covalent modality in proximity-induced drug pharmacology: Early development, current strategy, and feature directions

Abstract

With a growing number of covalent drugs securing FDA approval as successful therapies across various indications, particularly in the realm of cancer treatment, the covalent modulating strategy is undergoing a resurgence. The renewed interest in covalent bioactive compounds has captured significant attention from both the academic and biopharmaceutical industry sectors. Covalent chemistry presents several advantages over traditional noncovalent proximity-induced drugs, including heightened potency, reduced molecular size, and the ability to target "undruggable" entities. Within this perspective, we have compiled a comprehensive overview of current covalent modalities applied to proximity-induced molecules, delving into their advantages and drawbacks. Our aim is to stimulate more profound insights and ideas within the scientific community, guiding future research endeavors in this dynamic field.

Keywords: Bi-functional molecule; Covalent molecule; PROTAC; Proximity-induced drug.