Unlocking the "undruggable": current landscape and emerging frontiers in lysosomal receptor-mediated protein degradation - PubMed
3 hours ago
- #protein degradation
- #drug discovery
- #LYTAC
- Extracellular and membrane-associated proteins are challenging to target due to their 'undruggable' nature.
- Targeted protein degradation (TPD) technologies, like PROTACs, are limited to intracellular proteins.
- Lysosome-targeting chimeras (LYTACs) enable degradation of secreted and transmembrane proteins via the endocytosis-lysosomal pathway.
- LYTAC technology has evolved since 2020, incorporating various Lysosome-targeting receptor (LTR) strategies and delivery vehicles (aptamers, peptides, nanoparticles).
- LYTAC shows potential in oncology, neurological disorders, and immune-mediated diseases.
- Challenges include complex ligand design, immunogenicity risks, poor tissue selectivity, and limited clinical validation.
- Future research focuses on improving degradation efficiency, expanding disease applications, and clinical translation.