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Novel Design Strategies to Enhance the Efficiency of Proteolysis Targeting Chimeras

[Image: see text] Despite the success of drug discovery over the past decades, many potential drug targets still remain intractable for small molecule modulation. The development of proteolysis targeting chimeras (PROTACs) that trigger degradation of the target proteins provides a conceptually novel...

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Detalles Bibliográficos
Autores principales: Zhao, Chunlong, Dekker, Frank J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469497/
https://www.ncbi.nlm.nih.gov/pubmed/36110375
http://dx.doi.org/10.1021/acsptsci.2c00089
Descripción
Sumario:[Image: see text] Despite the success of drug discovery over the past decades, many potential drug targets still remain intractable for small molecule modulation. The development of proteolysis targeting chimeras (PROTACs) that trigger degradation of the target proteins provides a conceptually novel approach to address drug targets that remained previously elusive. Currently, the main challenge of PROTAC development is the identification of efficient, tissue- and cell-selective PROTAC molecules with good drug-likeness and favorable safety profiles. This review focuses on strategies to enhance the effectiveness and selectivity of PROTACs. We provide a comprehensive summary of recently reported PROTAC design strategies and discuss the advantages and disadvantages of these strategies. Future perspectives for PROTAC design will also be discussed.