A simple method for predicting serum protein binding of compounds from IC(50) shift analysis for in vitro assays.
Bioorg Med Chem Lett
; 14(9): 2309-12, 2004 May 03.
Article
em En
| MEDLINE
| ID: mdl-15081030
ABSTRACT
The shift in apparent IC(50) that attends addition of serum proteins to in vitro cellular, enzymatic, and receptor binding assays can be used to determine the dissociation constant for compound-serum protein complexes. We show here that a simple linear relationship exists between the apparent IC(50) in the presence of serum protein and the inverse of the apparent K(d) for the compound-serum protein complex. Using a series of cell-active kinase inhibitors we demonstrate that the K(d) value derived in this way can be used to predict the extent of protein binding in serum for various compounds. This method should provide a simple means of assessing the relative serum protein binding propensity of compounds early in the compound optimization phase of drug discovery campaigns.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Sanguíneas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2004
Tipo de documento:
Article