title: RSK2 Binding Models Delineate Key Features for Activity.
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.
authors: Information Technology Branch, Developmental Therapeutics Program, National Cancer Institute, Frederick, Maryland 21702 (USA).
authors: Rick
authors: R
authors: Gussio
authors: Michael J
authors: MJ
authors: Currens
authors: Dominic A
authors: DA
authors: Scudiero
authors: Jeffrey A
authors: JA
authors: Smith
authors: Deborah A
authors: DA
authors: Lannigan
authors: Robert H
authors: RH
authors: Shoemaker
authors: Dan W
authors: DW
authors: Zaharevitz
authors: Tam Luong
authors: TL
authors: Nguyen
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