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.
Original language | English |
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Pages (from-to) | 1229-1233 |
Number of pages | 5 |
Journal | Chemical Science |
Volume | 4 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2013 |
ASJC Scopus subject areas
- Chemistry(all)