design and optimization of Aurora A kinase inhibitors

Drug discovery programs urgently seek new chemical entities that meet the needs of a demanding pharmaceutical industry. Consequently, de novo ligand design is currently re-emerging as a novelty-generating approach. Using ligand-based de novo design software, we computationally generated, chemically...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2013-02, Vol.4 (3), p.1229-1233
Main Authors: Rodrigues, Tiago, Roudnicky, Filip, Koch, Christian P, Kudoh, Takayuki, Reker, Daniel, Detmar, Michael, Schneider, Gisbert
Format: Article
Language:English
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Summary:Drug discovery programs urgently seek new chemical entities that meet the needs of a demanding pharmaceutical industry. Consequently, de novo ligand design is currently re-emerging as a novelty-generating approach. Using ligand-based de novo design software, we computationally generated, chemically synthesized and biochemically tested a new arylsulfonamide against Aurora A kinase, a validated drug target in several types of cancer. The designed compound exhibited desired direct inhibitory activity against Aurora A kinase. By chemical optimization we obtained a lead structure exhibiting sustained activity in phenotypic assays. These results emphasize the potential of ligand-based de novo design to consistently deliver functional new chemotypes within short timeframes and limited effort. Using ligand-based de novo design software, we computationally generated, chemically synthesized and biochemically tested a new arylsulfonamide against Aurora A kinase, a validated drug target in several types of cancer.
ISSN:2041-6520
2041-6539
DOI:10.1039/c2sc21842a