De novo design and optimization of Aurora A kinase inhibitors

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Rodrigues, T; Roudnicky, F; Koch, CP; Kudoh, T; Reker, D; Detmar, M; Schneider, G

Published Date

  • March 1, 2013

Published In

Volume / Issue

  • 4 / 3

Start / End Page

  • 1229 - 1233

Electronic International Standard Serial Number (EISSN)

  • 2041-6539

International Standard Serial Number (ISSN)

  • 2041-6520

Digital Object Identifier (DOI)

  • 10.1039/c2sc21842a

Citation Source

  • Scopus