| Autor: |
Rick, Gussio, Michael J, Currens, Dominic A, Scudiero, Jeffrey A, Smith, Deborah A, Lannigan, Robert H, Shoemaker, Dan W, Zaharevitz, Tam Luong, Nguyen |
| Rok vydání: |
2011 |
| Předmět: |
|
| Zdroj: |
Journal of chemical and pharmaceutical research. 2(5) |
| ISSN: |
0975-7384 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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