AI Article Synopsis
- PROTAC (Proteolysis Targeting Chimera) is a developing technology that focuses on degrading specific proteins related to diseases, showing promise in both lab and clinical settings but facing challenges.
- Recent advances in targeted protein degradation (TPD) have introduced optimized strategies to address the limitations of conventional PROTACs, improving aspects like drug access, tissue selectivity, and control over the degradation process.
- The review outlines the progress in PROTAC technology, highlights improvements and new concepts, and aims to offer insights for future innovations and applications in drug design.
Article Abstract
Proteolysis Targeting Chimera (PROTAC) is an emerging and evolving technology based on targeted protein degradation (TPD). Small molecule PROTACs have shown great efficacy in degrading disease-specific proteins in preclinical and clinical studies, but also showed various limitations. In recent years, new technologies and advances in TPD have provided additional optimized strategies based on conventional PROTACs that can overcome the shortcomings of conventional PROTACs in terms of undruggable targets, bioavailability, tissue-specificity, spatiotemporal control, and degradation scope. In addition, some designs of special targeting chimeras and applications based on multidisciplinary science have shed light on novel therapeutic modalities and drug design. However, each improvement has its own advantages, disadvantages and application conditions. In this review, we summarize the exploration of PROTAC elements, depict a landscape of improvements and derived concepts of PROTACs, and expect to provide perspectives for technological innovations, combinations and applications in future targeting chimera design.
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| http://dx.doi.org/10.1016/j.biopha.2024.117584 | DOI Listing |
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