For the development of novel drugs against diseases such as cancer or inflammatory diseases, it is important to study processes in the body. To study these processes, inhibitors of enzymes can be used. By inhibiting an enzyme, we can learn about its function in healthy or diseased conditions. In this thesis, the discovery of inhibitors for two enzymes is described: Lysine Acetyltransferase 8 (KAT8) and Macrophage migration inhibitory factor (MIF). Four different types of inhibitors have been described for KAT8 and the mechanism of inhibition (how the inhibitors inhibit KAT8) for each of these inhibitors has been described. This resulted in remarkable differences in the mechanism between the different inhibitors. The mechanism can influence the way these inhibitors can (or can’t) be used in the development of novel drugs. This shows that it important to investigate the mechanism of enzyme inhibitors in an early stage of their development. Additionally, novel inhibitors for MIF have been described. These inhibitors may aid in the development of novel inhibitors against inflammatory diseases.
|Translated title of the contribution
|Kinetiek en remming van enzymen in een vroeg stadium van de ontwikkeling van geneesmiddelen: Een MOF en MIF symfonie
|Doctor of Philosophy
|Place of Publication
|Published - 2017