De novo design and optimization of Aurora A kinase inhibitors

TitleDe novo design and optimization of Aurora A kinase inhibitors
Publication TypeJournal Article
Year of Publication2013
AuthorsT Rodrigues, F Roudnicky, CP Koch, T Kudoh, D Reker, M Detmar, and G Schneider
JournalChem. Sci.
Volume4
Start Page1229
Issue3
Pagination1229 - 1233
Date Published03/2013
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. © 2013 The Royal Society of Chemistry.

DOI10.1039/c2sc21842a
Short TitleChem. Sci.