Novel cyclooxygenase-1 inhibitors discovered using affinity fingerprints.
J Med Chem
; 47(20): 4875-80, 2004 Sep 23.
Article
em En
| MEDLINE
| ID: mdl-15369391
ABSTRACT
We used protein affinity fingerprints to discover structurally novel inhibitors of cyclooxygenase-1 (COX-1) by screening a selected number of compounds, thus providing an alternative to extensive screening. From the affinity fingerprints of 19 known COX-1 inhibitors, a computational model for COX-1 inhibition was constructed and used to select candidate inhibitors from our compound library to be tested in the COX-1 assay. Subsequent refinement of the model by including affinity fingerprints of inactive compounds identified three molecules that were more potent than ibuprofen, a commonly used COX-1 inhibitor. These compounds are structurally distinct from those used to build the model and were discovered by testing only 62 library compounds. The discovery of these leads demonstrates the efficiency with which affinity fingerprints can identify novel bioactive chemotypes from known drugs.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de Ciclo-Oxigenase
/
Técnicas de Química Combinatória
/
Isoenzimas
/
Modelos Teóricos
Tipo de estudo:
Observational_studies
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article