A large number of cellular processes are regulated by the reversible conjugation of Ubiquitin (UB) proteins to substrates. UB-related research tools (including E1-, E2 and E3 Ligases) are now commercially available for further studying the role of this “Ubiquitin/Proteasome” pathway. Nevertheless, the identification of UB Ligase inhibitors remains challenging (1). Such bioactive small molecules are indeed important to further characterize the actors of this pathway, and to find new compounds for therapeutic applications.
Untill now, only a few bioactive molecules were characterized as Ub – Proteasome inhibitors. For example, TAME is known as a Ub-ligase inhibitor while Thialidomide and SMER3 specifically inhibit E3 UB ligase. (2-4)