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Updated: Oct 5, 2025
High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
Emerging targeted protein degradation tools for innovative drug discovery: From classical PROTACs to the novel and
Yue Zhong1, Fanglian Chi1, Hanyu Wu1
1Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, PR China.
Abstract:
Targeted protein degradation technology has evolved a brand-new therapeutic modality from an innovative drug discovery perspective. Though the classical PROTACs has pioneered the way for protein degraders, certain inherent defects such as poor druggability, uncontrollable catalysis caused off-targets, and limited E3 ubiquitin ligases available constitute obstacles that impede further advances. Recent medicinal chemists have preferred to investigate a type of optimized degraders beyond the classical PROTACs, bypassing such disadvantages to better facilitate targeted protein degradation. In this perspective, we comprehensively spotlighted the emerging approaches and techniques applied to the targeted protein degradation, specifically the PROTACs-derived strategies and other alternatives to realize protein degradation via proteasome or lysosome. Besides, contemporary confronted opportunities as well as challenges were further analyzed, with the aim to guide future discovery of novel protein degraders.
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