TY  - JOUR
A1  - Saleem, Rahman Shah Zaib
A1  - Schwalm, Martin P.
A1  - Knapp, Stefan
T1  - Expanding the ligand spaces for E3 ligases for the design of protein degraders
T2  - Bioorganic & medicinal chemistry
N2  - Targeted protein degradation (TPD) has recently emerged as an exciting new drug modality. However, the strategy of developing small molecule-based protein degraders has evolved over the past two decades and has now established molecular tags that are already in clinical use, as well as chimeric molecules, PROteolysis TArgeting Chimeras (PROTACs), based mainly on ligand systems developed for the two E3 ligases CRBN and VHL. The large size of the human E3 ligase family suggests that PROTACs can be developed by targeting a large diversity of E3 ligases, some of which have restricted expression patterns with the potential to design disease- or tissue-specific degraders. Indeed, many new E3 ligands have been published recently, confirming the druggability of E3 ligases. This review summarises recent data on E3 ligases and highlights the challenges in developing these molecules into efficient PROTACs rivalling the established degrader systems.
KW  - New E3-ligase ligands
KW  - PROTAC
KW  - Molecular glue
KW  - CRBN
KW  - VHL
KW  - Degrader design
Y1  - 2024
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/83759
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-837592
SN  - 0968-0896
VL  - 105
IS  - 117718
PB  - Elsevier
CY  - Amsterdam
ER  -