Current strategic trends in drug discovery: the present as prologue

Interplay of PROTAC Complex Dynamics for Undruggable Targets: Insights into Ternary Complex Behavior and Linker Design

“…Targeted protein degradation has become a pioneering paradigm in modern drug discovery with protein degraders, such as proteolysis-targeting chimeras (PROTACs), representing an innovative class of therapeutic agents that diverge significantly from conventional small molecule inhibitors. , Utilizing a unique strategy, PROTACs integrate bifunctional ligands binding to the target protein and an E3 ligase (E3L) to selectively degrade disease-associated proteins by directing them to the ubiquitin–proteasome system . PROTACs span a wide therapeutic spectrum encompassing oncology, neurodegenerative diseases, cardiovascular disorders, infectious diseases, autoimmune conditions, metabolic disorders, hormonal imbalances, inflammatory disorders, and rare genetic diseases. , In ongoing clinical trials, around 26 PROTAC compounds are currently under investigation, and Arvinas and Pfizer’s Vepdegestrant (ARV-471) has been granted FDA Fast Track designation for the treatment of ER + /HER2 – metastatic breast cancer. , …”