Effects of Pimozide Derivatives on pSTAT5 in K562 Cells

Maria Meli, Antonio Cascio, Rosaria Maria Pipitone, Stefania Grimaudo, Martina Maccesi, Riccardo Rondanin, Daniele Simoni, Romeo Romagnoli, Daniele Simoni

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10 Citations (Scopus)

Abstract

STAT5 is a transcription factor, a member of the STAT family of signaling proteins. STAT5 is involved in many types of cancer, including chronic myelogenous leukemia (CML), in which this protein is found constitutively activated as a consequence of BCR-ABL expression. The neuroleptic drug pimozide was recently reported to act as an inhibitor of STAT5 phosphorylation and is capable of inducing apoptosis in CML cells in vitro. Our research group has synthesized simple derivatives of pimozide with cytotoxic activity and that are able to decrease the levels of phosphorylated STAT5. In this work we continued the search for novel STAT5 inhibitors, synthesizing compounds in which the benzoimidazolinone ring of pimozide is either maintained or modified, in order to obtain further structure–activity relationship information for this class of STAT5 inhibitors. Two compounds of the series showed potent cytotoxic activity against BCR-ABL-positive and pSTAT5-overexpressing K562 cells and were able to markedly decrease the levels of phosphorylated STAT5.
Original languageEnglish
Pages (from-to)1183-1190
Number of pages8
JournalChemMedChem
Volume12
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology
  • Drug Discovery
  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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    Meli, M., Cascio, A., Pipitone, R. M., Grimaudo, S., Maccesi, M., Rondanin, R., Simoni, D., Romagnoli, R., & Simoni, D. (2017). Effects of Pimozide Derivatives on pSTAT5 in K562 Cells. ChemMedChem, 12, 1183-1190.