title: Computational design and discovery of "minimally structured" hERG blockers.
abstract: Molecular knowledge of hERG blocking liability can offer the possibility of optimizing lead compounds in a way that eliminates potentially lethal side effects. In this study, we computationally designed, synthesized, and tested a small series of "minimally structured" molecules. Some of these compounds were remarkably potent against hERG (6, IC(50) = 2.4 nM), allowing us to identify the minimal structural requirements for hERG blocking liability.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy. andrea.cavalli@unibo.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Rosa
authors.initials: R
authors.lastname: Buonfiglio
authors.forename: Cristina
authors.initials: C
authors.lastname: Ianni
authors.forename: Matteo
authors.initials: M
authors.lastname: Masetti
authors.forename: Luisa
authors.initials: L
authors.lastname: Ceccarini
authors.forename: Rachel
authors.initials: R
authors.lastname: Caves
authors.forename: Michael W Y
authors.initials: MW
authors.lastname: Chang
authors.forename: John S
authors.initials: JS
authors.lastname: Mitcheson
authors.forename: Marinella
authors.initials: M
authors.lastname: Roberti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
mesh_terms: D015195:Drug Design; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D026902:Potassium Channel Blockers / Q000009:adverse effects / Q000138:chemical synthesis*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers