Receptor–ligand interaction-based virtual screening for novel Eg5/Kinesin spindle protein inhibitors

Nagarajan, S., Skoufias, D.A., Kozielski, F. and Pae, A.N. (2012) Receptor–ligand interaction-based virtual screening for novel Eg5/Kinesin spindle protein inhibitors. Journal of Medicinal Chemistry, 55(6), pp. 2561-2573. (doi: 10.1021/jm201290v)

Abstract

Eg5/KSP is a promising mitotic spindle target for drug discovery in cancer chemotherapy and the development of agents against fungal diseases. A range of Eg5 targeting compounds identified by in vitro or cell-based screening is currently in development. We employed structure-based virtual screening of a database of 700 000 compounds to identify three novel Eg5 inhibitors bearing quinazoline (24) or thioxoimidazolidine (30 and 37) scaffolds. The new compounds inhibit Eg5 ATPase activity, show growth inhibition in proliferation assays, and induce monoastral spindles in cells, the characteristic phenotype for Eg5 inhibiting agents. This is the first successful reported procedure for the identification of Eg5 inhibitors via receptor–ligand interaction-based virtual screening.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kozielski, Professor Frank
• Authors: Nagarajan, S., Skoufias, D.A., Kozielski, F., and Pae, A.N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Medicinal Chemistry
• ISSN: 0022-2623
• Published Online: 06 February 2012