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Updated: Jul 15, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
Targeted degradation of extracellular secreted and membrane proteins
Xuankun Chen1, Yaxian Zhou1, Yuan Zhao1
1Lachman Institute for Pharmaceutical Development, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.
Abstract:
Targeted protein degradation (TPD) involving chimeric molecules has emerged as one of the most promising therapeutic modalities in recent years. Among various reported TPD strategies, proteolysis-targeting chimeras (PROTACs) stand out as a significant breakthrough in small-molecule drug discovery and have garnered the most attention to date. However, PROTACs are mainly capable of depleting intracellular proteins. Given that many important therapeutic targets such as cytokines, growth factors, and numerous receptors are membrane proteins or secreted extracellularly, there is interest in the development of novel strategies to degrade these protein categories. We review advances in this emerging area and provide insights to enhance the development of novel TPDs targeting extracellular proteins.
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