title: Vorinostat-like molecules as structural, stereochemical, and pharmacological tools.
abstract: The inhibitory activity of an ω-alkoxy analogue of the HDAC inhibitor, Vorinostat (SAHA), against the 11 isoforms of HDAC is described and evaluated with regard to structural biology information retrieved through computational methods. Preliminary absorption and metabolism studies were performed, which positioned this compound as a potential candidate for further preclinical studies and delineated measures for improving its pharmacokinetic profile.
authors.affiliation: Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Centre-ville, Montréal, QC, H3C 3J7, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
authors.affiliation: Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Centre-ville, Montréal, QC, H3C 3J7, Canada ; Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Traversa La Crucca 3, I-07040 Sassari, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Auzzas
authors.affiliation: Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Centre-ville, Montréal, QC, H3C 3J7, Canada ; Department of Chemistry, Umeå University, 901 87, Umeå, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Centre-ville, Montréal, QC, H3C 3J7, Canada.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Sigma-Tau Research & Development, Via Pontina Km 30.400, I-00040 Pomezia, Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.affiliation: Sigma-Tau Research & Development, Via Pontina Km 30.400, I-00040 Pomezia, Roma, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Gallo
authors.affiliation: Sigma-Tau Research & Development, Via Pontina Km 30.400, I-00040 Pomezia, Roma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciacci
authors.affiliation: Sigma-Tau Research & Development, Via Pontina Km 30.400, I-00040 Pomezia, Roma, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
keywords: HDAC promiscuous inhibitors; HDAC1−11 profile; SAHA analogues; absorption and metabolism; class IIa-specific profile