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

STATs are transcription factors acting as intracellular signaling after stimulation with cytokines, growthfactors and hormones. STAT5 is also constitutively active in many forms of cancers, including chronicmyelogenous leukemia, acute lymphoblastic leukemia and Hodgkin’s lymphoma. Recently, literaturereported that the neuroleptic drug pimozide inhibits STAT5 phosphorylation inducing apoptosis inCML cells. We undertook an investigation from pimozide structure, obtaining simple derivatives withcytotoxic and STAT5-inhibitory activity, two of them markedly more potent than pimozide.