Discovery and characterization of novel TRPML1 agonists.
Bioorg Med Chem Lett
; 98: 129595, 2024 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-38141860
ABSTRACT
Screening a library of >100,000 compounds identified the substituted tetrazole compound 1 as a selective TRPML1 agonist. Both enantiomers of compound 1 were separated and profiled in vitro and in vivo. Their selectivity, ready availability and CNS penetration should enable them to serve as the tool compounds of choice in future TRPML1 channel activation studies. SAR studies on conformationally locked macrocyclic analogs further improved the TRPML1 agonist potency while retaining the selectivity.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tetrazóis
/
Canais de Potencial de Receptor Transitório
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article