Search results for "STAT5 inhibitor"
showing 5 items of 5 documents
THE ANTINEOPLASTIC ROLE OF STAT5 INHIBITION IN BCRABL1-POSITIVE CELLS EXPOSED TO PIMOZIDE ALONE AND IN COMBINATION WITH DASATINIB AND PONATINIB
2021
EVEN though the last decades have seen the success of the targeted treatments for BCRABL1-positive Chronic Myeloid Leukemia (CML), with the outstanding achievement of placing selected patients into the so called treatment-free remission, a minor part of these subjects face TKI resistance and/or intolerance. Resistance is a challenging point in the clinical management of CML, occurring in approximately 10–20% of CML cases, due to several mechanisms, among which point mutations of the BCR‐ABL kinase domain, BCRABL overexpression or alternative splicing, sub-efficient plasma concentration of the inhibitor and abnormal drug efflux/influx. The Signal Transducer and Activators of Transcription (S…
Inhibition of activated STAT5 in Bcr/Abl expressing leukemia cells with new pimozide derivatives.
2014
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.
Novel iodoacetamido benzoheterocyclic derivatives with potent antileukemic activity are inhibitors of STAT5 phosphorylation
2016
Signal Transducer and Activator of Transcription 5 (STAT5) protein, a component of the STAT family of signaling proteins, is considered to be an attractive therapeutic target because of its involvement in the progression of acute myeloid leukemia. In an effort to discover potent molecules able to inhibit the phosphorylation-activation of STAT5, twenty-two compounds were synthesized and evaluated on the basis of our knowledge of the activity of 2-(3’,4’,5’-trimethoxybenzoyl)-3-iodoacetamido-6-methoxy benzo[b]furan derivative 1 as a potent STAT5 inhibitor. Most of these molecules, structurally related to compound 1, were characterized by the presence of a common 3’,4’,5’-trimethoxybenzoyl moi…
STAT5 and STAT5 Inhibitors in Hematological Malignancies
2019
The JAK-STAT pathway is an important physiologic regulator of different cellular functions including proliferation, apoptosis, differentiation, and immunological responses. Out of six different STAT proteins, STAT5 plays its main role in hematopoiesis and constitutive STAT5 activation seems to be a key event in the pathogenesis of several hematological malignancies. This has led many researchers to develop compounds capable of inhibiting STAT5 activation or interfering with its functions. Several anti-STAT5 molecules have shown potent STAT5 inhibitory activity in vitro. However, compared to the large amount of clinical studies with JAK inhibitors that are currently widely used in the clini…
Effects of Pimozide Derivatives on pSTAT5 in K562 Cells
2017
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 benzoimidazol…