Mapping Biological Activities to Different Types of Molecular Scaffolds: Exemplary Application to Protein Kinase Inhibitors
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Scaffolds were originally introduced to delineate core structures of active compounds. They are also used to assess the ability of computational methods to identify structurally diverse active compounds. Biological activities of compound series are often mapped to scaffolds. This is done to better understand activity distributions over different structural classes or search for core structures of compounds that are preferentially active against target families of interest. Herein, we describe in detail how such scaffold activity profiles are generated and compare profiles for differently defined scaffolds. As an exemplary application, scaffolds of currently available kinase inhibitors covering the human kinome are analyzed.
Key wordsBioactive compounds Scaffolds Core structures Scaffold–activity relationships Kinase inhibitors Compound promiscuity
We thank OpenEye Scientific Software, Inc. for a free academic license of the OpenEye Toolkits.
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