Discovery of inhibitors of the pentein superfamily protein dimethylarginine dimethylaminohydrolase (DDAH), by virtual screening and hit analysis.
Bioorg Med Chem Lett
; 17(14): 3953-6, 2007 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-17543521
ABSTRACT
An efficient process for the discovery of inhibitors of DDAH enzymes, without the requirement for high throughput screening, is described. Physicochemical filtering of a 308,000-compound library according to drug likeness followed by reciprocal nearest neighbour selection produced a representative subset of 35,000 compounds. Virtual screening on a dual processor PC using FlexX, followed by biological screening, identified two hit series. Similarity searches of commercial databases and chemical re-synthesis of pure compounds resulted in SR445 as an inhibitor of Pseudomonas aeruginosa DDAH at 2 microM.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
/
Inibidores Enzimáticos
/
Amidoidrolases
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2007
Tipo de documento:
Article