RESUMEN
A set of arylazopyrazole-based inhibitors targeting the mitotic motor protein CENP-E was discovered through the chemical platform using the quantitative cyclization of 1,3-diketone intermediate with various hydrazines under mild conditions. Through this efficient platform, the structure-activity relationship pertaining to the pyrazole photoswitch in photoswitchable CENP-E inhibitors not only in vitro but also in cells was successfully clarified.
Asunto(s)
Proteínas Cromosómicas no Histona , Pirazoles , Ciclización , Pirazoles/química , Pirazoles/farmacología , Pirazoles/síntesis química , Relación Estructura-Actividad , Humanos , Proteínas Cromosómicas no Histona/antagonistas & inhibidores , Proteínas Cromosómicas no Histona/metabolismo , Estructura Molecular , Compuestos Azo/química , Compuestos Azo/farmacología , Compuestos Azo/síntesis química , Relación Dosis-Respuesta a DrogaRESUMEN
An arylazopyrazole-based covalent inhibitor targeting the mitotic motor protein of centromere-associated protein E (CENP-E) was developed. Using this photoswitchable inhibitor, a photoswitchable CENP-E was chemically constructed in cells, which enabled to local control of mitotic cell division with light illumination.