RSK2 Binding Models Delineate Key Features for Activity.
J Chem Pharm Res
; 2(5): 587-598, 2010.
Article
em En
| MEDLINE
| ID: mdl-21593990
ABSTRACT
Due to its overexpression and activation in human cancer cells and tissues, an emerging molecular target in cancer therapeutics is p90 ribosomal s6 kinase 2 (RSK2). While a growing number of RSK2 inhibitors have been reported in the literature, only the crystal structure of RSK2 in complex with an AMP analogue provides a structural basis for understanding RSK2 inhibition. To remedy this, we used our fluorescence polarization assay to determine the RSK2 activity for a set of structurally diverse compounds, and followed this by modeling their binding modes in an all-atom, energy refined crystal structure of RSK2. These binding models reveal that Val131 and Leu147 are key interaction sites for potent RSK2 inhibition. This structure-based pharmacophore is an important tool for new lead discovery and refinement.
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MEDLINE
Idioma:
En
Revista:
J Chem Pharm Res
Ano de publicação:
2010
Tipo de documento:
Article