A Selective Modulator of Peroxisome Proliferator-Activated Receptor γ with an Unprecedented Binding Mode.
J Med Chem
; 63(9): 4555-4561, 2020 05 14.
Article
em En
| MEDLINE
| ID: mdl-32267688
ABSTRACT
The nuclear peroxisome proliferator-activated receptor γ has well-validated therapeutic potential in metabolic, inflammatory, and neurodegenerative pathologies, but its activation is also associated with marked adverse effects and novel modes of PPARγ modulation are required. Here, we report the discovery and profiling of a new PPARγ modulator chemotype endowed with remarkable potency and a distinct binding mode in the orthosteric PPARγ ligand-binding site. Its R-enantiomer evolved as a eutomer regarding PPARγ activation with a high eudysmic ratio. The new PPARγ modulator revealed outstanding selectivity over the PPARα and PPARδ subtypes and did not promote adipogenesis in primary human fibroblasts, discriminating it from established agonists.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
PPAR gama
/
Benzotiazóis
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha