title: Polyamine-based small molecule epigenetic modulators.
abstract: Chromatin remodelling enzymes such as the histone deacetylases (HDACs) and histone demethylases such as lysine-specific demethylase 1 (LSD1) have been validated as targets for cancer drug discovery. Although a number of HDAC inhibitors have been marketed or are in human clinical trials, the search for isoform-specific HDAC inhibitors is an ongoing effort. In addition, the discovery and development of compounds targeting histone demethylases are in their early stages. Epigenetic modulators used in combination with traditional antitumor agents such as 5-azacytidine represent an exciting new approach to cancer chemotherapy. We have developed multiple series of HDAC inhibitors and LSD1 inhibitors that promote the re-expression of aberrantly silenced genes that are important in human cancer. The design, synthesis and biological activity of these analogues is described herein.
authors.affiliation: Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, 48202, USA.
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Stuart
authors.initials: S
authors.lastname: Hazeldine
authors.forename: Michael L
authors.initials: ML
authors.lastname: Crowley
authors.forename: Allison
authors.initials: A
authors.lastname: Hanson
authors.forename: Ross
authors.initials: R
authors.lastname: Beattie
authors.forename: Sheeba
authors.initials: S
authors.lastname: Varghese
authors.forename: Thulani M D
authors.initials: TM
authors.lastname: Senanayake
authors.forename: Aiko
authors.initials: A
authors.lastname: Hirata
authors.forename: Fusao
authors.initials: F
authors.lastname: Hirata
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.forename: Nora
authors.initials: N
authors.lastname: Steinbergs
authors.forename: Tracey
authors.initials: T
authors.lastname: Murray-Stewart
authors.forename: Ian
authors.initials: I
authors.lastname: Bytheway
authors.forename: Robert A
authors.initials: RA
authors.lastname: Casero
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Woster