RESUMEN
Directed screening has identified a novel series of MMP13 inhibitors that possess good levels of activity whilst possessing excellent selectivity over related MMPs. The binding mode of the series has been solved by co-crystallisation and demonstrates an interesting mode of inhibition without interaction with the catalytic zinc atom.
Asunto(s)
Inhibidores de la Metaloproteinasa de la Matriz , Inhibidores de Proteasas/química , Zinc/química , Sitios de Unión , Dominio Catalítico , Cristalografía por Rayos X , Metaloproteinasa 13 de la Matriz/metabolismo , Inhibidores de Proteasas/síntesis química , Inhibidores de Proteasas/farmacología , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
A novel approach to inhibition of the alphavbeta3 integrin is described, which uses compounds designed to generate nM potency without using the arginine binding site.
Asunto(s)
Integrina alfaVbeta3/antagonistas & inhibidores , Animales , Sitios de Unión , Simulación por Computador , Diseño de Fármacos , Humanos , Integrina alfaVbeta3/metabolismo , Oligopéptidos/química , Ratas , Bibliotecas de Moléculas Pequeñas , Relación Estructura-ActividadRESUMEN
A number of molecular recognition features have been exploited in structure-based design of selective Cathepsin inhibitors.
Asunto(s)
Catepsinas/antagonistas & inhibidores , Inhibidores de Proteasas/química , Catepsinas/metabolismo , Simulación por Computador , Cristalografía por Rayos X , Diseño de Fármacos , Inhibidores de Proteasas/síntesis química , Inhibidores de Proteasas/farmacología , Relación Estructura-ActividadRESUMEN
A series of potent Cathepsin L inhibitors with good selectivity with respect to other cysteine Cathepsins is described and SAR is discussed with reference to the crystal structure of a protein-ligand complex.