Strategies to discover unexpected targets for drugs active at G protein-coupled receptors.
Annu Rev Pharmacol Toxicol
; 51: 117-44, 2011.
Article
en En
| MEDLINE
| ID: mdl-20868273
G protein-coupled receptors (GPCRs) are an evolutionarily conserved family of signaling molecules comprising approximately 2% of the human genome; this receptor family remains a central focus in basic pharmacology studies and drug discovery efforts. Detailed studies of drug action at GPCRs over the past decade have revealed existing and novel ligands that exhibit polypharmacology-that is, drugs with activity at more than one receptor target for which they were designed. These "off-target" drug actions can be a liability that causes adverse side effects; however, in several cases, drugs with less selectivity demonstrate better clinical efficacy. Here we review physical screening and cheminformatic approaches that define drug activity at the GPCR receptorome. In many cases, such profiling has revealed unexpected targets that explain therapeutic actions as well as off-targets underlying drug side effects. Such drug-receptor profiling has also provided new insights into mechanisms of action of existing drugs and has suggested directions for future drug development.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Sistemas de Liberación de Medicamentos
/
Receptores Acoplados a Proteínas G
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Annu Rev Pharmacol Toxicol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos