Selective and Potent PROTAC Degraders of c-Src Kinase.
ACS Chem Biol
; 19(1): 110-116, 2024 01 19.
Article
in En
| MEDLINE
| ID: mdl-38113191
ABSTRACT
Using dasatinib linked to E3 ligase ligands, we identified a potent and selective dual Csk/c-Src PROTAC degrader. We then replaced dasatinib, the c-Src-directed ligand, with a conformation-selective analogue that stabilizes the αC-helix-out conformation of c-Src. Using the αC-helix-out ligand, we identified a PROTAC that is potent and selective for c-Src. We demonstrated a high degree of catalysis with our c-Src PROTACs. Using our c-Src PROTACs, we identified pharmacological advantages of c-Src degradation compared to inhibition with respect to cancer cell proliferation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ubiquitin-Protein Ligases
Language:
En
Journal:
ACS Chem Biol
Year:
2024
Document type:
Article
Affiliation country:
United States