RESUMEN

In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo.

Asunto(s)

Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Histona Desacetilasas , Cetonas/química , Antineoplásicos/uso terapéutico , Quelantes/farmacología , Química Farmacéutica , Diseño de Fármacos , Inhibidores Enzimáticos/farmacología , Células HeLa , Humanos , Modelos Químicos , Neoplasias/tratamiento farmacológico , Profármacos/química , Relación Estructura-Actividad , Zinc/química