Imperial College London

PROTACs, molecular glues and bifunctionals from bench to bedside


The ubiquitin-proteasome system (UPS) is one of the main regulatory mechanisms for protein homeostasis in eukaryotes. (B) The catalytic MOA of PROTACs involves the formation of a key ternary complex

Congratulations to four of our group members who have published a book chapter reviewing the field of protein degradation, glues and bifbifunctionals

The review: PROTACs, molecular glues and bifunctionals from bench to bedside: unlocking the clinical potential of catalytic drugs is part of the book series Progress in Medicinal Chemistry published by Science Direct and was written by postdocs Maria Maneiro, Elena De Vita and Daniel Conole and PhD students Cyrille Kounde and Qisi Zhang.  

PROteolysis TArgeting Chimeras (PROTACs) are small molecule degraders that are bifunctional, allowing them to bind both a protein of interest and the cell’s machinery for degradation. This dual modality means that they can be used to effectively target specific proteins for removal from the cell.  

The chapter covers the history of PROTAC development alongside discussion of the experimental progress made to understand these new compounds and common strategies for their design, providing comprehensive coverage of the literature to date in this area. The field of PROTAC research has recently seen molecules progress to clinical trials and the review also covers the pharmacokinetic and pharmacodynamic considerations that this has involved alongside an introduction to the biotech landscape that has resulted from this expanding area.

The review concludes with discussion of the next steps for the area of targeted protein degradation and other emerging areas of scientific interest triggered by the invention of PROTACs.


Jennie Hutton

Jennie Hutton
Department of Chemistry

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