Exploring the chemical space of orally bioavailable PROTACs.
Drug Discov Today
; 29(4): 103917, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38360147
ABSTRACT
A principal challenge in the discovery of proteolysis targeting chimeras (PROTACs) as oral medications is their bioavailability. To facilitate drug design, it is therefore essential to identify the chemical space where orally bioavailable PROTACs are more likely to be situated. To this aim, we extracted structure-bioavailability insights from published data using traditional 2D descriptors, thereby shedding light on their potential and limitations as drug design tools. Subsequently, we describe cutting-edge experimental, computational and hybrid design strategies based on 3D descriptors, which show promise for enhancing the probability of discovering PROTACs with high oral bioavailability.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Descoberta de Drogas
/
Quimera de Direcionamento de Proteólise
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article