title: Integration of ligand and structure-based virtual screening for the identification of the first dual targeting agent for heat shock protein 90 (Hsp90) and tubulin.
abstract: We describe the discovery of a novel indazole-based scaffold that represents the "first-in-class" dual Hsp90/tubulin binding compound. Individual known ligands for both targets shared similar 3',4',5'-trimethoxyphenyl cores, and from this it was hypothesized that application of an integrated ligand and structure-based virtual screening (VS) workflow could yield a single scaffold with dual binding affinity. Following validation of the VS protocol, we successfully identified a novel dual inhibitor, sourced from a commercial screening collection of 160 000 compounds.
authors.affiliation: Molecular Design Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Knox
authors.forename: Trevor
authors.initials: T
authors.lastname: Price
authors.forename: Michal
authors.initials: M
authors.lastname: Pawlak
authors.forename: Georgia
authors.initials: G
authors.lastname: Golfis
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Flood
authors.forename: Darren
authors.initials: D
authors.lastname: Fayne
authors.forename: D Clive
authors.initials: DC
authors.lastname: Williams
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Meegan
authors.forename: David G
authors.initials: DG
authors.lastname: Lloyd