Small molecules that allosterically inhibit p21-activated kinase activity by binding to the regulatory p21-binding domain
Experimental & Molecular Medicine
;
: e229-2016.
Artigo
em Inglês
| WPRIM
| ID: wpr-137227
ABSTRACT
p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity. These molecules interfere with the interactions between the p21-binding domain (PBD) of PAK1 and Rho GTPases by binding to the PBD. Importantly, they inhibit the activity of full-length PAKs and are selective for PAK1 and PAK3 in vitro and in living cells. These compounds may potentially be useful for determining the details of the PAK signaling pathway and may also be used as lead molecules in the development of more selective and potent PAK inhibitors.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosfotransferases
/
Técnicas In Vitro
/
Sobrevivência Celular
/
Programas de Rastreamento
/
Actinas
/
Proteínas rho de Ligação ao GTP
/
Proliferação de Células
/
Quinases Ativadas por p21
/
Doenças do Sistema Nervoso
Tipo de estudo:
Estudo de rastreamento
Limite:
Humanos
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2016
Tipo de documento:
Artigo
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