VR23 is a chloroquine derivative that functions as a proteasome inhibitor (IC50s = 1 nM, 50-100 nM, and 3 μM for trypsin-like, chymotrypsin-like, and caspase-like proteasomes, respectively). 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. In combination with the chymotrypsin-like proteasome inhibitor bortezomib , VR23 can produce a synergistic effect in killing multiple myeloma cells, including those that are resistant to bortezomib.
