Proteolysis Targeting Chimeras (PROTACs) have fundamentally changed the landscape of drug discovery by introducing targeted oncogenic protein degradation as an innovative therapeutic strategy. As opposed to traditional small-molecule inhibitors that block protein function, PROTACs facilitate the selective degradation of disease-causing proteins, including those commonly considered "undruggable", presenting novel avenues for medical intervention. Recent strides in chemistry, biology, and computational methods have accelerated the evolution of next-generation PROTACs with improved cell permeability, tissue specificity, and reduced off-target effects (minimized side effects).
This Research Topic aims to delve into pioneering advancements and future prospects in PROTAC-based therapeutics. As the field continues to grow, PROTACs are demonstrating significant promise in oncology, along with expanding applications to non-oncological diseases. Our goal is to capture the full spectrum of ongoing research, from foundational strategies to practical applications, with a focus on discovering novel targets, unraveling mechanistic insights, and employing innovative drug discovery techniques.
This Research Topic invites submissions exploring breakthroughs and future trajectories in the development of PROTACs, with contributions concentrated in the following areas:
• PROTAC-Based Therapeutics: Strategies leveraging targeted protein degradation to address hard-to-treat cancers, highlighting case studies, mechanistic investigations, and clinical implications.
• Drug Discovery Opportunities: Exploring novel avenues for small molecules, including molecular glues or targeted therapies that can be applied in diverse pathophysiological settings.
• Challenges and Perspectives: Addressing pivotal challenges such as stability, delivery modalities, drug resistance, and immune system interactions, alongside opportunities for technological and methodological improvement.
• Expanding PROTAC Utility: Discussing the transition from traditional enzyme inhibition to modern targeted protein degradation, expanding the therapeutic utility of PROTAC technology.
• Drug Design Evolution: Highlighting structure-based and AI-informed approaches in drug discovery, enhancing the development of both inhibitors and novel degraders.
Keywords: PROTAC, Proteolysis Targeting Chimeras, protein degradation, oncology therapeutics, drug discovery
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
