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New kinase inhibitors
Hakrová, Kateřina ; Nencka, Radim (advisor) ; Tichý, Michal (referee)
Acute myeloid leukemia (AML) is a heterogenous malignancy characterized by the occurrence of common myeloid progenitors, which then accumulate in the bone marrow and peripheral blood. This subsequently leads to a failure of hematopoiesis. Approximately one third of patients have a mutation in FMS-like tyrosine kinase (FLT3), which is associated with a higher risk of relapse and an overall worse prognosis. In recent years, several FLT3 inhibitors have been developed to facilitate the treatment of AML but patients develop resistance to most of them over time, leading to subsequent relapse of the disease. This bachelor's thesis discusses the synthesis of new potential inhibitors and the effect of imidazo[1,2-b]pyridazine core substitution on the inhibitory activity of these substances against the internal tandem duplication (ITD) type mutation in FLT3 kinase. Key words: AML, FLT3, imidazo[1,2-b]pyridazine, kinase inhibitors
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Effect of CDK and FLT3 inhibitors on activity of ABC efflux transporters in vitro, relation to multidrug resistance
Poráč, Jakub ; Čečková, Martina (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jakub Poráč Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Effect of CDK and FLT3 inhibitors on activity of ABC efflux transporters in vitro, relation to multidrug resistance P-gp and BCRP are transmembrane proteins that form part of a large family of ABC transporters. These are ATP-driven transporters, which main task is to eliminate exogenous and endogenous substances and their metabolites from cells of both, healthy and tumour tissues. This activity is often associated with the expulsion of administered therapeutics and multiple drug resistance (MDR) in tumour cells. A promising therapy of cancer represents a newer class of drugs target the tyrosine kinase (TK), and cyclin-dependent kinases (CDK), which are cell enzymes responsible for the processes of proliferation, apoptosis and differentiation. Cyclin- dependent kinase inhibitors (CDKI) are used in the treatment of breast cancer, but at the same time they form a new group of drugs with the potential for use in hematological malignancies. In the treatment of AML, a new successful approach is TK inhibitors (TKI), which target the mutated FLT3 receptor, specifically the recently approved drugs midostaurin and...
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Effect of CDK and FLT3 inhibitors on activity of ABC efflux transporters in vitro, relation to multidrug resistance
Poráč, Jakub ; Čečková, Martina (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jakub Poráč Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Effect of CDK and FLT3 inhibitors on activity of ABC efflux transporters in vitro, relation to multidrug resistance P-gp and BCRP are transmembrane proteins that form part of a large family of ABC transporters. These are ATP-driven transporters, which main task is to eliminate exogenous and endogenous substances and their metabolites from cells of both, healthy and tumour tissues. This activity is often associated with the expulsion of administered therapeutics and multiple drug resistance (MDR) in tumour cells. A promising therapy of cancer represents a newer class of drugs target the tyrosine kinase (TK), and cyclin-dependent kinases (CDK), which are cell enzymes responsible for the processes of proliferation, apoptosis and differentiation. Cyclin- dependent kinase inhibitors (CDKI) are used in the treatment of breast cancer, but at the same time they form a new group of drugs with the potential for use in hematological malignancies. In the treatment of AML, a new successful approach is TK inhibitors (TKI), which target the mutated FLT3 receptor, specifically the recently approved drugs midostaurin and...
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