posted on 2005-03-28, 00:00authored byBernard Pirard, Joachim Brendel, Stefan Peukert
Different virtual screening techniques are available as alternatives to high throughput screening. These different
techniques have been rarely used together on the same target. We had the opportunity to do so in order to
discover novel blockers of the voltage-dependent potassium channel Kv1.5, a potential target for the treatment
of atrial fibrillation. Our corporate database was searched, using a protein-based pharmacophore, derived
from a homology model, as query. As a result, 244 molecules were screened in vitro, 19 of them (7.8%)
were found to be active. Five of them, belonging to five different chemical classes, exhibited IC50 values
under 10 μM. The performance of this structure-based virtual screening protocol has been compared with
those of similarity and ligand-based pharmacophore searches. The analysis of the results supports the
conventional wisdom of using as many virtual screening techniques as possible in order to maximize the
chance of finding as many chemotypes as possible.