RESUMEN
Piperidinyl diphenylsulfonyl sulfonamides are a novel class of molecules that have inhibitory binding affinity for sFRP-1. As a secreted protein sFRP-1 inhibits the function of the secreted Wnt glycoprotein. Therefore, as inhibitors of sFRP-1 these small molecules facilitate the Wnt/beta-catenin canonical signaling pathway. Details of the structure-activity relationships and biological activity of this structural class of compounds will be discussed.
Asunto(s)
Glicoproteínas/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Sulfonamidas/química , Sulfonamidas/farmacología , Proteínas Wnt/metabolismo , Animales , Línea Celular Tumoral , Glicoproteínas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Ratones , Microsomas Hepáticos/metabolismo , Técnicas de Cultivo de Órganos , Osteogénesis/efectos de los fármacos , Ratas , Cráneo/citología , Cráneo/efectos de los fármacos , Relación Estructura-Actividad , beta Catenina/metabolismoRESUMEN
The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related disorders. Details of the structure-activity relationships and biological activity from the first structural class of this scaffold will be discussed.