Design, synthesis, and evaluation of BTK-targeting PROTACs with optimized bioavailability in vitro and in vivo.
RSC Med Chem
; 14(8): 1562-1566, 2023 Aug 16.
Article
em En
| MEDLINE
| ID: mdl-37593574
ABSTRACT
Ibrutinib is a first-line drug for the treatment of B-cell malignancies. BTKC481S mutation has led to drug resistance during clinical application. Herein, a novel BTK-targeting PROTAC molecule with better solubility and bioavailability was developed. Compound 15-271 has better solubility than ibrutinib and some reported BTK PROTACs. 15-271 has better liver microsomal stability than its analogues in multiple species. More importantly, 15-271 has a longer half-life and better bioavailability in vivo. The development strategy of compound 15-271 can be a general procedure for the optimization of other PROTACs.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
RSC Med Chem
Ano de publicação:
2023
Tipo de documento:
Article