Issue 3, 2013

De novo design and optimization of Aurora A kinase inhibitors

Abstract

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.

Graphical abstract: De novo design and optimization of Aurora A kinase inhibitors

Supplementary files

Article information

Article type
Edge Article
Submitted
27 Oct 2012
Accepted
19 Dec 2012
First published
14 Jan 2013

Chem. Sci., 2013,4, 1229-1233

De novo design and optimization of Aurora A kinase inhibitors

T. Rodrigues, F. Roudnicky, C. P. Koch, T. Kudoh, D. Reker, M. Detmar and G. Schneider, Chem. Sci., 2013, 4, 1229 DOI: 10.1039/C2SC21842A

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