New Generation of PROTACs: Advancement in Light-Responsive and Self-Assembled PROTACs

The burgeoning field of targeted protein degradation has witnessed significant advancements with the development of proteolysis-targeting chimeras (PROTACs). This mini-review aims to provide an insightful overview of the latest advancements in cancer therapy, particularly the evolution of stimuli-responsive, controlled, self-assembled PROTACs. We explore a spectrum of innovative developments, including photo-responsive PROTACs, near-infrared-activated PROTACs, and those that functions based on biorthogonal reactions. The emergence of polymer-based PROTACs is also highlighted, underscoring their improved efficacy and specificity. Despite their potential, these novel approaches face significant challenges, particularly in clinical translation. This review underscores the achievements of these ground-breaking technologies and the hurdles that must be overcome to realize their full therapeutic potential. Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to targeted protein degradation, particularly in cancer therapy. This review highlights the latest advancements in stimuli-responsive and self-assembled PROTACs, including light-activated and polymer-based systems, while addressing challenges in clinical translation. With their potential to enhance treatment specificity and efficacy, PROTACs are poised to redefine the future of targeted cancer therapies. image