Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Sci Rep ; 12(1): 13520, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941181

RESUMO

SMIFH2 is a small molecule inhibitor of the formin family of cytoskeletal regulators that was originally identified in a screen for suppression of actin polymerization induced by the mouse formin Diaphanous 1 (mDia1). Despite widespread use of this compound, it is unknown whether SMIFH2 inhibits all human formins. Additionally, the nature of protein/inhibitor interactions remains elusive. We assayed SMIFH2 against human formins representing six of the seven mammalian classes and found inhibitory activity against all formins tested. We synthesized a panel of SMIFH2 derivatives and found that, while many alterations disrupt SMIFH2 activity, substitution of an electron-donating methoxy group in place of the bromine along with halogenation of the furan ring increases potency by approximately five-fold. Similar to SMIFH2, the active derivatives are also pan-inhibitors for the formins tested. This result suggests that while potency can be improved, the goal of distinguishing between highly conserved FH2 domains may not be achievable using the SMIFH2 scaffold.


Assuntos
Actinas , Proteínas de Transporte , Tionas/farmacologia , Uracila/análogos & derivados , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Animais , Proteínas de Transporte/metabolismo , Citoesqueleto/metabolismo , Forminas , Humanos , Mamíferos/metabolismo , Camundongos , Estrutura Terciária de Proteína , Uracila/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA