Discovery of N-(4-Aminobutyl)-N'-(2-methoxyethyl)guanidine as the First Selective, Nonamino Acid, Catalytic Site Inhibitor of Human Dimethylarginine Dimethylaminohydrolase-1 (hDDAH-1).
J Med Chem
; 63(1): 425-432, 2020 01 09.
Article
em En
| MEDLINE
| ID: mdl-31841335
ABSTRACT
N-(4-Aminobutyl)-N'-(2-methoxyethyl)guanidine (8a) is a potent inhibitor targeting the hDDAH-1 active site (Ki = 18 µM) and derived from a series of guanidine- and amidine-based inhibitors. Its nonamino acid nature leads to high selectivities toward other enzymes of the nitric oxide-modulating system. Crystallographic data of 8a-bound hDDAH-1 illuminated a unique binding mode. Together with its developed N-hydroxyguanidine prodrug 11, 8a will serve as a most widely applicable, pharmacological tool to target DDAH-1-associated diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores Enzimáticos
/
Amidoidrolases
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Guanidinas
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article