Efficient, multi-hundred-gram scale access to E3 ubiquitin ligase ligands for degrader development.
Org Biomol Chem
; 21(41): 8344-8352, 2023 10 25.
Article
em En
| MEDLINE
| ID: mdl-37800999
ABSTRACT
Small molecule heterobifunctional degraders (commonly also known as PROTACs) offer tremendous potential to deliver new therapeutics in areas of unmet medical need. To deliver on this promise, a new discipline directed at degrader design and optimization has emerged within medicinal chemistry to address a central challenge, namely how to optimize relatively large, heterobifunctional molecules for activity, whilst maintaining drug-like properties. This process involves simultaneous optimization of the three principle degrader components E3 ubiquitin ligase ligand, linker, and protein of interest (POI) ligand. A substantial degree of commonality exists with the E3 ligase ligands typically used at the early stages of degrader development, resulting in demand for these compounds as chemical building blocks in degrader research programs. We describe herein a collation of large scale, high-yielding syntheses to access the most utilized E3 ligase ligands to support early-stage degrader development.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Ubiquitina-Proteína Ligases
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article