PROTAC technology: A new drug design for chemical biology with many challenges in drug discovery

Target Protein Degradation TPD is a new avenue and revolutionary for therapeutics because redefining the principles of classical drug discovery and guided by event-based target activity rather than the occupancy-driven activity. Since the discovery of the first PROTAC in 2001, TPD represents a rapidly growing technology, with applications in both drug discovery and chemical biology. Over the last decade, many questions have been raised and today the knowledge gained by each team has elucidated a number of them, although there is still a long way to go. The objective of this work is to present the challenges that the PROTAC strategy has very recently addressed in drug design and discovery by presenting extremely recent results from the literature and to provide guidelines in the drug design of new PROTACs as successful therapeutic modality for medicinal chemists.