Inhibition of activated STAT5 in Bcr/Abl expressing leukemia cells with new pimozide derivatives

Bioorg Med Chem Lett. 2014 Sep 15;24(18):4568-4574. doi: 10.1016/j.bmcl.2014.07.069.

Riccardo Rondanin ¹, Daniele Simoni ², Romeo Romagnoli ², Riccardo Baruchello ², Paolo Marchetti ², Cristiana Costantini ², Sara Fochi ², Giacomo Padroni ², Stefania Grimaudo ³, Rosaria Maria Pipitone ³, Maria Meli ⁴, Manlio Tolomeo ⁵

Affiliations

1 Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy. Electronic address: rnd@unife.it.
2 Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy.
3 Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy.
4 Dipartimento di Scienze per la Promozione della Salute e Materno Infantile, Area di Farmacologia, Università di Palermo, Palermo, Italy.
5 Centro Interdipartimentale di Ricerca in Oncologia Clinica e Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Malattie Infettive, Università di Palermo, Palermo, Italy.

PMID: 25131537 DOI: 10.1016/j.bmcl.2014.07.069

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.

Keywords

Apoptosis; BCR/ABL expressing leukemia; Cell growth inhibition; Pimozide; STAT5 inhibitors.

Name
Email *

	Sorry, but the email address you supplied was invalid.