Inhibition of 19S proteasome-associated deubiquitinases by metal-containing compounds

Copper and gold complexes have clinical activity in several diseases including cancer. Recently, we have reported that the anti-cancer activity of copper (II) pyrithione CuPT and gold (I) complex auranofin is associated with targeting the 19S proteasome-associated deubiquitinases (DUBs), UCHL5 and USP14. Here we discuss metal DUB inhibitors in treating cancer and other diseases. (from Editor). Several copper and gold complexes have clinical activity in treating some human diseases including cancer. Recently, we have reported that the anti-cancer activity of copper (II) pyrithione CuPT and gold (I) complex auranofin is tightly associated with their ability to target and inhibit the 19S proteasome-associated deubiquitinases (DUBs), UCHL5 and USP14. In this article we review small molecule inhibitors of DUBs and 19S proteasome-associated DUBs. We then describe and discuss the ubique nature of CuPT and auranofin, which is inhibition of 19S proteasome-associated UCHL5 and USP14. We finally suggest the potential to develop novel, specific metal-based DUB inhibitors for treating cancer and other diseases