Related Experiment Video
Updated: Jun 27, 2025
05:33
High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
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CYpHER: Catalytic extracellular targeted protein degradation with high potency and durable effect
Zachary R Crook1,2,3, Gregory P Sevilla1,2,3, Pamela Young2
1Cyclera Therapeutics Inc, Seattle, WA 98115, USA. Present address of Z.R.C., G.P.S., and N.W.N.
Biorxiv : the Preprint Server for Biology
|May 7, 2024
Summary
CYpHER technology offers a novel approach to targeted protein degradation (TPD) by utilizing pH-dependent endolysosomal delivery and recycling. This method enhances drug potency and reduces off-target risks for treating diseases like cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Conventional inhibitors often fail to address multiple pathogenic mechanisms of disease-causing proteins.
- Targeted protein degradation (TPD) offers a strategy to eliminate disease proteins by hijacking cellular machinery.
- Existing TPD strategies involve E3 ligases or endolysosomal pathway uptake.
Conclusions:
- CYpHER technology provides a potent and durable TPD strategy.
- Its pH-dependent and TfR-mediated mechanism offers advantages in efficacy and safety.
- CYpHER shows promise for treating EGFR-driven cancers and other TfR-expressing tumors.
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