|Title||De novo design and optimization of Aurora A kinase inhibitors|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||T Rodrigues, F Roudnicky, CP Koch, T Kudoh, D Reker, M Detmar, and G Schneider|
|Pagination||1229 - 1233|
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.
|Short Title||Chem. Sci.|