UBE2N: Hope on the Cancer Front, How to Inhibit This Promising Target Prospect?

UBE2N protein belongs to the UE2s family and plays a crucial role in DNA repair, making it an exciting target for the development of innovative anticancer therapies. With the aim of discovering UBE2N inhibitors (UBE2Ni), this perspective seeks to review and provide elements to guide the design of new compounds. We propose a chemoinformatic structural analysis of the protein and its areas of interaction with its different partners. While covalent UBE2Ni are the most advanced molecules in their development, noncovalent inhibitors offer significant advantages that could overcome the limitations of covalent ones, particularly in terms of selectivity. Lastly, to obtain a drug candidate, early assessment of the druggability of compounds is essential in a hit to lead process. For existing UBE2Ni, a critical challenge lies in their pharmacokinetic properties and will obviously have to be considered as early as possible to hope for an application in human therapy.