VR23

VR23 is a potent and selective inhibitor of trypsin-like proteasomes (IC₅₀ = 1 nmol/L), chymotrypsin-like proteasomes (IC₅₀ = 50-100 nmol/L), and caspase-like proteasomes (IC₅₀ = 3 μmol/L). The main molecular target of VR23 was β2 of the 20S proteasome catalytic subunit. It also deregulates the activity of cyclin E and other centrosomal proteins, resulting in the induction of multiple centrosome amplification, abnormal spindle formation, uneven cytokinesis, irreversible mitotic arrest, and eventually apoptosis that is specific to cancer cells.