Virtual screening approach for the identification of new Rac1 inhibitors.
Rac1 protein is implicated in several events of atherosclerotic plaque development and represents a new potential pharmacological target for cardiovascular diseases. In this paper we describe a pharmacophore virtual screening followed by molecular docking calculations leading to the identification of five new Rac1 inhibitors. These compounds were shown to be more effective than the reference compound NSC23766 in reducing the intracellular levels of Rac1-GTP, thus supporting this approach for the development of new Rac1 inhibitors.
Ferri
Nicola
N
Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, 20133 Milano, Italy. nicola.ferri@unimi.it
Corsini
Alberto
A
Bottino
Paolo
P
Clerici
Francesca
F
Contini
Alessandro
A
D016475:3T3 Cells; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry
D004791:Enzyme Inhibitors; D020830:rac1 GTP-Binding Protein