Search results for "STAT5 inhibitors"

showing 3 items of 3 documents

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.

Clinical BiochemistryFusion Proteins bcr-ablPharmaceutical ScienceApoptosisBiochemistrySettore MED/15 - Malattie Del SangueCell LineStructure-Activity RelationshipPimozideSettore BIO/13 - Biologia Applicatahemic and lymphatic diseasesDrug DiscoverymedicineSTAT5 Transcription FactorCytotoxic T cellHumansPhosphorylationMolecular BiologyTranscription factorSTAT5Cell ProliferationbiologyDose-Response Relationship DrugMolecular StructureChemistrySTAT5 inhibitorsPimozideBCR/ABL expressing leukemia ApoptosisCell growth inhibitionOrganic ChemistryCell CyclePimozidemedicine.diseaseSettore CHIM/08 - Chimica FarmaceuticaLeukemiaApoptosisCancer researchbiology.proteinSettore BIO/14 - FarmacologiaMolecular MedicinePhosphorylationK562 Cellsmedicine.drugChronic myelogenous leukemia
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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…

0301 basic medicineApoptosisAntineoplastic Agentchemistry.chemical_compoundBenzophenone0302 clinical medicinehemic and lymphatic diseasesFuranDrug DiscoverySTAT5 Transcription FactorTumor Cells CulturedThiopheneMoietyPhosphorylationSTAT5Molecular StructurebiologyChemistryBiological activityGeneral MedicineApoptosis; BCR/ABL expressing leukemia; In vitro antiproliferative activity; STAT5 inhibitors; Structure-activity relationship; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; PharmacologyLeukemia Myeloid Acute030220 oncology & carcinogenesisBCR/ABL expressing leukemiaApoptosis; BCR/ABL expressing leukemia; In vitro antiproliferative activity; STAT5 inhibitors; Structure-activity relationship; Antineoplastic Agents; Apoptosis; Benzofurans; Benzophenones; Cell Proliferation; Dose-Response Relationship Drug; Drug Screening Assays Antitumor; Humans; K562 Cells; Leukemia Myeloid Acute; Molecular Structure; Phosphorylation; STAT5 Transcription Factor; Structure-Activity Relationship; Tumor Cells Cultured; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; PharmacologyHumanStereochemistryAntineoplastic AgentsArticleNOBenzophenones03 medical and health sciencesK562 CellHumansStructure–activity relationshipBenzofuransCell ProliferationPharmacologyIndole testDose-Response Relationship DrugIn vitro antiproliferative activitySTAT5 inhibitorsDrug Discovery3003 Pharmaceutical ScienceOrganic ChemistryApoptosiSTAT5 inhibitorStructure-activity relationshipIn vitro030104 developmental biologybiology.proteinBenzofuranDrug Screening Assays AntitumorK562 Cells
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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…

0301 basic medicineantiproliferationApoptosisPharmacologyBiochemistryAntineoplastic Agent0302 clinical medicinePimozidehemic and lymphatic diseasesDrug DiscoverySTAT5 Transcription FactorCytotoxic T cellPhosphorylationGeneral Pharmacology Toxicology and PharmaceuticsBCR-ABL-expressing leukemia; STAT5 inhibitors; antiproliferation; apoptosis; pimozideSTAT5Molecular StructurebiologyPimozidefood and beverages030220 oncology & carcinogenesisMolecular MedicinePhosphorylationHumanmedicine.drugAntineoplastic AgentsNOStructure-Activity Relationship03 medical and health sciencesK562 CellmedicineHumansTranscription factorCell ProliferationPharmacologyDose-Response Relationship DrugCell growthSTAT5 inhibitorsOrganic ChemistryApoptosiSTAT5 inhibitormedicine.disease030104 developmental biologyPharmacology Toxicology and Pharmaceutics (all)biology.proteinCancer researchBCR-ABL-expressing leukemiaDrug Screening Assays AntitumorK562 CellsK562 cellsChronic myelogenous leukemiaChemMedChem
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