title: Inhibition of activated STAT5 in Bcr/Abl expressing leukemia cells with new pimozide derivatives.
abstract: STATs are transcription factors acting as intracellular signaling after stimulation with cytokines, growth factors and hormones. STAT5 is also constitutively active in many forms of cancers, including chronic myelogenous leukemia, acute lymphoblastic leukemia and Hodgkin's lymphoma. Recently, literature reported that the neuroleptic drug pimozide inhibits STAT5 phosphorylation inducing apoptosis in CML cells. We undertook an investigation from pimozide structure, obtaining simple derivatives with cytotoxic and STAT5-inhibitory activity, two of them markedly more potent than pimozide.
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy. Electronic address: rnd@unife.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rondanin
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Simoni
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy.
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Baruchello
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Costantini
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Fochi
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Padroni
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy.
authors.forename: Rosaria Maria
authors.initials: RM
authors.lastname: Pipitone
authors.affiliation: Dipartimento di Scienze per la Promozione della Salute e Materno Infantile, Area di Farmacologia, Università di Palermo, Palermo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Meli
authors.affiliation: Centro Interdipartimentale di Ricerca in Oncologia Clinica e Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Malattie Infettive, Università di Palermo, Palermo, Italy.
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D010766:Phosphorylation / Q000187:drug effects; D010868:Pimozide / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D050799:STAT5 Transcription Factor; D010868:Pimozide; D016044:Fusion Proteins, bcr-abl
keywords: Apoptosis; BCR/ABL expressing leukemia; Cell growth inhibition; Pimozide; STAT5 inhibitors