Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.
Nat Rev Drug Discov
; 18(10): 770-796, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31388135
ABSTRACT
Phosphodiesterases (PDEs), enzymes that degrade 3',5'-cyclic nucleotides, are being pursued as therapeutic targets for several diseases, including those affecting the nervous system, the cardiovascular system, fertility, immunity, cancer and metabolism. Clinical development programmes have focused exclusively on catalytic inhibition, which continues to be a strong focus of ongoing drug discovery efforts. However, emerging evidence supports novel strategies to therapeutically target PDE function, including enhancing catalytic activity, normalizing altered compartmentalization and modulating post-translational modifications, as well as the potential use of PDEs as disease biomarkers. Importantly, a more refined appreciation of the intramolecular mechanisms regulating PDE function and trafficking is emerging, making these pioneering drug discovery efforts tractable.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
/
Transdução de Sinais
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3',5'-AMP Cíclico Fosfodiesterases
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Terapia de Alvo Molecular
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Rev Drug Discov
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido