Synthesis of protein-kinase inhibitors as a potential treatment of cancer

Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry in collaboration with Biomedical Research Center UH HK Author: Sara Merdita Supervisor: Assoc. Prof. PharmD. Jaroslav Roh, PhD. Advisors: PharmD. Lukáš Górecki, PhD.; Assoc. Prof. PharmD. Jan Korábečný, PhD. Title of diploma thesis: Synthesis of protein-kinase inhibitors as a potential treatment for cancer Cancer is one of the leading causes of fatalities worldwide, which is attracting attention of many researchers with desire to develop treatments that selectively target cancerous cells while simultaneously sparing healthy cells. The main overall strategy is to exploit features specific to cancer - the cancer hallmarks. Those are represented, for instance, by genomic instability and aberrant DNA damage response (DDR) pathways. The DDR consists of cascades of kinases and other proteins and messengers, where we highlighted the synthetic lethal interaction between the kinases ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related). The two are major driving forces in the DDR, where in cancer ATM tends to be mutated and therefore dysfunctional, making the cells' viability reliant on ATR. Thus, ATR inhibition makes a particularly attractive strategy for abrogating cancer survival without..