Ligand-based and structure-based virtual screening to identify carbonic anhydrase IX inhibitors.
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.
Thiry
Anne
A
Drug Design and Discovery Center, FUNDP, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium. anne.thiry@fundp.ac.be
Ledecq
Marie
M
Cecchi
Alessandro
A
Frederick
Raphael
R
Dogné
Jean-Michel
JM
Supuran
Caudiu T
CT
Wouters
Johan
J
Masereel
Bernard
B
D000951:Antigens, Neoplasm / Q000187:drug effects*; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects*; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; D008024:Ligands; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases