A Novel Lysosome Targeting Chimera for Targeted Protein Degradation via Split-and-Mix Strategy
Citations Over TimeTop 10% of 2024 papers
Abstract
Targeted protein degradation is becoming more and more important in the field of drug development. Compared with proteasomal-based degraders, lysosomal-based degraders have a broader target spectrum of targets, which have been demonstrated to have great potential, especially in degrading undruggable proteins. Recently, we developed a programmable and facile screening PROTAC development platform based on peptide self-assembly termed split-and-mix PROTAC (SM-PROTAC). In this study, we applied this technology for the development of lysosome-based degraders, named a split-and-mix chaperone-mediated autophagy-based degrader (SM-CMAD). We successfully demonstrated SM-CMAD as a universal platform by degrading several targets, including ERα, AR, MEK1/2, and BCR-ABL. Different from other lysosomal-based degraders, SM-CMAD was capable of facile screening with programmable ligand ratios. We believe that our work will promote the development of other multifunctional molecules and clinical translation for lysosomal-based degraders.
Related Papers
- Roles of autophagy in lymphocytes： reflections and directions(2010)
- Death and survival of neuronal and astrocytic cells in ischemic brain injury： a role of autophagy(2011)
- Autophagy and cardiovascular diseases(2013)
- → Is Selective Autophagy Distinct from Starvation-Induced Autophagy?(2016)
- Autophagy in cancer biology and therapy(2014)