Current Status of Drug Discovery and Development Through Targeted Protein Degradation

Abstract

In recent years, drug discovery research utilizing targeted protein degradation (TPD), which enables the selective elimination of specific intracellular and extracellular proteins, has attracted considerable attention. Compounds that induce TPD leverage multiple degradation mechanisms within the endogenous cellular proteasome and lysosome pathway. Among these, the clinical application of chimeric degraders represented by PROTAC^Ⓡ (Proteolysis Targeting Chimera) has advanced rapidly in recent years, approaching the stage of social implementation. However, during the clinical development process, several common challenges related to physicochemical properties and pharmacokinetics for practical application have also emerged. This article provides an overview of TPD technologies followed by the current status of clinical trials for chimeric degraders and discusses the issues that have emerged so far and future prospects for overcoming them.