title: Imidazo[2,1-b]thiazole guanylhydrazones as RSK2 inhibitors.
abstract: The activity of a series of imidazo[2,1-b]thiazole guanylhydrazones as inhibitors of p90 ribosomal S6 kinase 2 (RSK2) is described. It was found that a small subset of compounds show both potent inhibition of RSK2 kinase activity and tumor cell growth in vitro. Detailed study of one of the most active compounds indicates a high degree of selectivity for inhibition of RSK2 compared to a spectrum of other related kinases. Selective inhibition of the MCF-7 breast tumor cell line compared to MCF-10A non-transformed cells, as well as selective inhibition of the biomarker GSK3 provides evidence that the compounds can affect the RSK2 target in cells.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. aldo.andreani@unibo.it
authors.forename: Aldo
authors.initials: A
authors.lastname: Andreani
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Granaiola
authors.forename: Alberto
authors.initials: A
authors.lastname: Leoni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Locatelli
authors.forename: Rita
authors.initials: R
authors.lastname: Morigi
authors.forename: Mirella
authors.initials: M
authors.lastname: Rambaldi
authors.forename: Lucilla
authors.initials: L
authors.lastname: Varoli
authors.forename: Deborah
authors.initials: D
authors.lastname: Lannigan
authors.forename: Jeff
authors.initials: J
authors.lastname: Smith
authors.forename: Dominic
authors.initials: D
authors.lastname: Scudiero
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kondapaka
authors.forename: Robert H
authors.initials: RH
authors.lastname: Shoemaker
mesh_terms: D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors*; D013055:Spectrophotometry, Infrared
chemical_list: D004791:Enzyme Inhibitors; D006835:Hydrazones; D019893:Ribosomal Protein S6 Kinases; D038362:Glycogen Synthase Kinase 3