0000000001002366

AUTHOR

Yvette Hoehn

showing 2 related works from this author

The kinase inhibitor LS104 induces apoptosis, enhances cytotoxic effects of chemotherapeutic drugs and is targeting the receptor tyrosine kinase FLT3…

2008

Activating mutations of FLT3 are found in approximately one-third of acute myeloid leukemia (AML)-cases and are considered to represent an attractive therapeutic target. In this study, we report that the hydroxystyryl-acrylonitrile compound LS104 inhibits proliferation and induces potent cytotoxic effects in FLT3 expressing leukemic cells in vitro. Immunoblot and phosphoprotein-FACS analysis demonstrated inhibiton of phosphorylation of FLT3-ITD and of its downstream targets. In pharmacokinetic studies, a rapid and dose dependent cellular uptake of LS104 lasting up to 11h could be demonstrated. Combination of LS104 with chemotherapeutic agents markedly enhanced cytotoxic effects. Recently, a…

AdultMaleCancer ResearchDaunorubicinmedicine.drug_classBlotting WesternFluorescent Antibody TechniqueApoptosisPharmacologyReceptor tyrosine kinaseTyrosine-kinase inhibitorStyrenesColony-Forming Units AssayMiceBone Marrowhemic and lymphatic diseasesAntineoplastic Combined Chemotherapy ProtocolsmedicineTumor Cells CulturedCD135AnimalsHumansPoint MutationTissue DistributionAgedCell ProliferationAged 80 and overbiologyAcrylonitrileDaunorubicinCytarabineMyeloid leukemiaCell DifferentiationHematologyMiddle Agedmedicine.diseaseLeukemiaLeukemia Myeloid AcuteOncologyfms-Like Tyrosine Kinase 3Fms-Like Tyrosine Kinase 3Cytarabinebiology.proteinCancer researchDrug Therapy CombinationFemalemedicine.drugSignal TransductionLeukemia research
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LS104, a Novel Kinase Inhibitor, Induces Apoptosis, Synergizes with Cytostatic Drugs and Is Targeting the Receptor Tyrosine Kinase FLT3.

2005

Abstract Fms-like tyrosine kinase 3 (FLT3), a member of the class III tyrosine kinase receptor family, is expressed in up to 90% of acute myeloid leukemia (AML). Activating mutations like internal tandem duplication (ITD) of the juxtamembrane domain and kinase domain point mutations are found in approximately 35% of AML-cases and are considered to represent an attractive therapeutic target. In this study, we report that the novel hydroxystyryl-acrylonitrile compound LS104 induces potent cytotoxic effects in FLT3 ITD-positive leukemic cells. As a cellular model to investigate FLT3-ITD specific effects we used 32D myeloid cells stably transfected with FLT3-ITD and wt-FLT3, respectively. In MT…

KinaseCell growthImmunologyTyrosine phosphorylationCell BiologyHematologyBiologymedicine.diseaseBiochemistryMolecular biologyReceptor tyrosine kinaseLeukemiachemistry.chemical_compoundchemistryAnnexinhemic and lymphatic diseasesembryonic structuresmedicinebiology.proteinKinase activityTyrosineBlood
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