Yehudit Morozovsky defended her bachelor's thesis
Larisa Ivanova
On June 2, 2025, Yehudit Morozovsky defended her bachelor’s thesis. The thesis focused on the development of new potential AlkBH5 inhibitor using different computational methods. AlkBH5 is a mammalian demethylase responsible for removal of m6A (N6-methyladenosine) modification in RNA. The multiple roles of AlkBH5 in various human diseases, including cancer and non-cancer conditions make it perspective molecular target for the development of new drugs. As has been shown by different studies, the regulation of AlkBH5 activity using small-molecule ligands can have the therapeutic potential. In this work, a dataset of new compounds was developed based on the structure of the previously reported AlkBH5 inhibitors, the best-performing newly designed compounds were used for the similarity search of the commercially available compounds database. The combined approach and several-step validation process allowed us to identify the 3 most promising compounds. Further biological evaluation showed that one of the identified compounds has in vitro activity against recombinant AlkBH5, as well as antiproliferative activity against one cancer cell line. In addition, Yehudit’s work highlighted the importance of the validation of 3D structure of the target protein, docking software, as well as the selection criteria. In sum, this work provides useful insights into the structural features of the AlkBH5 inhibitors as well as into the impact of the software used on the molecular docking and MD simulation results. Together, all these findings can provide a solid basis for the further development of new AlkBH5 inhibitors.
The thesis was supervised by Dr. Larisa Ivanova.
