Design of isoform-selective inhibitors of nitric oxide synthase.
Curr Opin Chem Biol
; 2(4): 491-500, 1998 Aug.
Article
em En
| MEDLINE
| ID: mdl-9736922
ABSTRACT
Nitric oxide synthase, the mammalian enzyme catalyzing the oxidation of L-arginine to L-citrulline and nitric oxide, is present in three isoforms that have distinct physiological roles. Overstimulation or overexpression of individual nitric oxide synthase isoforms plays a role in a wide range of disorders including septic shock, arthritis, diabetes, ischemia-reperfusion injury, pain and various neurodegenerative diseases. Animal studies and early clinical trials suggest that nitric oxide synthase inhibitors could be therapeutic in many of these disorders, but preservation of physiologically important nitric oxide synthase functions might require use of isoform-selective inhibitors. Within the past few years both amino acid and nonamino acid nitric oxide synthase inhibitors with pharmacologically useful isoform selectivity have been reported. Selectivity has been achieved on the basis of initial binding affinity and, for mechanism-based inactivators, on the basis of isoform-dependent catalytic activation; particularly interesting are N5-(1-imino-3-butenyl)-L-ornithine, ARL 17477, 1400W and S-(2-aminoethyl)isothiourea.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arginina
/
Desenho de Fármacos
/
Óxido Nítrico Sintase
/
Inibidores Enzimáticos
/
Isoenzimas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Opin Chem Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos