Studium inhibice ABC lékových efluxních transportérů vybranými inhibitory tyrozinkináz pomocí akumulačních metod s cytostatickými substráty

Suchá, Simona

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Simona Suchá Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study of ABC drug efflux transporter inhibition by selected tyrosine kinase inhibitors using accumulation methods with cytostatic substrates ATP-binding cassette (ABC) drug efflux transporters are transmembrane proteins that utilize the energy from ATP hydrolysis to drive transport of endogenous and exogenous compounds out of the cell. The overexpression of ABC transporters plays a crucial role in the development of multidrug resistance (MDR), a phenomenon responsible for the failure of chemotherapy. Tyrosine kinase inhibitors (TKI) represent novel beneficial therapeutic approach in cancer treatment. TKI block tyrosine kinases which regulate important cellular processes. Deregulation of these enzymes can lead to various types of cancers. In the present work, we investigated interaction potential of selected TKI (alectinib, brivanib, osimertinib, selumetinib) in MDCKII parent cell line and those transduced with human efflux transporters ABCB1, ABCC1 and ABCG2. Using the accumulation studies, we determined the amount of accumulated model substrates (daunorubicin, mitoxantrone) and evaluated the inhibitory effect of...

host :: přihlásit Digitální repozitář
		Hledej		Nový záznam		Nápověda		O repozitáři