title: Spotting and designing promiscuous ligands for drug discovery.
abstract: The promiscuous binding behavior of bioactive compounds forms a mechanistic basis for understanding polypharmacological drug action. We present the development and prospective application of a computational tool for identifying potential promiscuous drug-like ligands. In combination with computational target prediction methods, the approach provides a working concept for rationally designing such molecular structures. We could confirm the multi-target binding of a de novo generated compound in a proof-of-concept study relying on the new method.
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland. gisbert.schneider@pharma.ethz.ch and inSili.com LLC, Segantinisteig 3, 8049 Zürich, Switzerland. info@insili.com.
authors.forename: P
authors.initials: P
authors.lastname: Schneider
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland. gisbert.schneider@pharma.ethz.ch.
authors.forename: M
authors.initials: M
authors.lastname: Röthlisberger
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland. gisbert.schneider@pharma.ethz.ch.
authors.forename: D
authors.initials: D
authors.lastname: Reker
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland. gisbert.schneider@pharma.ethz.ch.
authors.forename: G
authors.initials: G
authors.lastname: Schneider
mesh_terms: D055808:Drug Discovery; D008024:Ligands
chemical_list: D008024:Ligands