Discovery of a new series of PI3K-δ inhibitors from Virtual Screening.
Bioorg Med Chem Lett
; 42: 128046, 2021 06 15.
Article
em En
| MEDLINE
| ID: mdl-33865969
ABSTRACT
PI3K-δ mediates key immune cell signaling pathways and is a target of interest for treatment of oncological and immunological disorders. Here we describe the discovery and optimization of a novel series of PI3K-δ selective inhibitors. We first identified hits containing an isoindolinone scaffold using a combined ligand- and receptor-based virtual screening workflow, and then improved potency and selectivity guided by structural data and modeling. Careful optimization of molecular properties led to compounds with improved permeability and pharmacokinetic profile, and high potency in a whole blood assay.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ftalimidas
/
Descoberta de Drogas
/
Classe I de Fosfatidilinositol 3-Quinases
/
Inibidores de Fosfoinositídeo-3 Quinase
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article