Ligand-based and structure-based virtual screening to identify carbonic anhydrase IX inhibitors

Anne Thiry; Marie Ledecq; Alessandro Cecchi; Raphael Frederick; Jean-Michel Dogné; Caudiu T Supuran; Johan Wouters; Bernard Masereel

doi:10.1016/j.bmc.2008.11.071

Ligand-based and structure-based virtual screening to identify carbonic anhydrase IX inhibitors

Bioorg Med Chem. 2009 Jan 15;17(2):553-7. doi: 10.1016/j.bmc.2008.11.071. Epub 2008 Dec 6.

Authors

Anne Thiry¹, Marie Ledecq, Alessandro Cecchi, Raphael Frederick, Jean-Michel Dogné, Caudiu T Supuran, Johan Wouters, Bernard Masereel

Affiliation

¹ Drug Design and Discovery Center, FUNDP, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium. anne.thiry@fundp.ac.be

PMID: 19097911
DOI: 10.1016/j.bmc.2008.11.071

Abstract

A three-dimensional pharmacophore model of CA IX inhibitors was generated and used to screen the ZINC database of commercially available compounds. The hits were docked in a CA IX homology model. By visualizing the binding mode and score of these compounds, six derivatives were selected and evaluated for their inhibitory potency against CA IX. A highly active CA IX inhibitor was identified which may be used as a lead to design novel such derivatives.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Neoplasm / drug effects*
Carbonic Anhydrase IX
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / drug effects*
Computer Simulation
Drug Discovery / methods*
Drug Evaluation, Preclinical
Humans
Ligands
Protein Binding
Structure-Activity Relationship

Substances

Antigens, Neoplasm
Carbonic Anhydrase Inhibitors
Ligands
CA9 protein, human
Carbonic Anhydrase IX
Carbonic Anhydrases