Epigenetic Drug Discovery: Bromodomain Inhibitors

Bromodomains are one of many proteins tasked with regulating certain genes. They have been of great interest as drug targets due to their connection to diseases such as cancer. Despite the significant amount of work that has gone into developing inhibitors that prevent their binding activity, two compounds have yet to be explored as potential inhibitors. Using three different approaches to Fragment-based Drug Design, we have elaborated on N-Methylpyrrolidone and 5-methyl-3-aryl-1H-pyrazole as potential bromodomain inhibitor candidates. This work has resulted in the development of several lead compounds with improved inhibition and crystal structures that have helped rationalise their activity.