Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center.
FEBS Lett
; 586(19): 3410-4, 2012 Sep 21.
Article
em En
| MEDLINE
| ID: mdl-22841723
ABSTRACT
We have used boron-based molecules to create novel, competitive, reversible inhibitors of phosphodiesterase 4 (PDE4). The co-crystal structure reveals a binding configuration which is unique compared to classical catechol PDE4 inhibitors, with boron binding to the activated water in the bimetal center. These phenoxybenzoxaboroles can be optimized to generate submicromolar potency enzyme inhibitors, which inhibit TNF-α, IL-2, IFN-γ, IL-5 and IL-10 activities in vitro and show safety and efficacy for topical treatment of human psoriasis. They provide a valuable new route for creating novel potent anti-PDE4 inhibitors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
/
Compostos de Boro
/
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos