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Novel structures with a potential to inhibit FLT3 receotir: In vitro evaluation using AML cell lines
Zídková, Anna ; Čečková, Martina (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Zídková Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Consultant: Mgr. Jan Rataj Title of diploma thesis: Novel structures with a potential to inhibit the FLT3 receptor: In vitro evaluation using AML cell lines Acute myeloid leukemia (AML) is a rapidly progressing hematologic malignancy, characterized by the proliferation and accumulation of immature myeloblasts in the bone marrow and peripheral blood. Despite significant achievements, treatment outcomes remain unsatisfactory. Mutations in the FLT-3 (FMS-like tyrosine kinase 3) gene are detected in up to one-third of patients with newly diagnosed AML, contributing to the poor prognosis of the disease. FLT-3 inhibitors thus represent a new approach to targeted therapy. Although they have only recently been introduced into therapy, resistance to them is already being developed by leukemic cells, often resulting in treatment failure. In this study, we aimed to test 8 newly synthesized compounds as potential FLT-3 inhibitors and to evaluate their possible contribution in overcoming resistance to the clinically used FLT-3 inhibitor gilteritinib. Using the MTT method, the ability of these compounds to induce cell death was tested in the...

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