A Novel Proteasome Inhibitor (NPI-0052)

NPI-0052 was discovered during the fermentation of Salinospora tropica, a new marine actinomycete. The compound offers significant possibilities in the treatment of many cancers. NPI-0052 is a potent inhibitor of the human 20S proteasome and, in in vitro studies, is more potent and selective than Velcade, the first proteasome inhibitor approved by the FDA. The success of Velcade in the treatment of multiple myeloma provides evidence that proteasome inhibitors can be effective clinically. However, resistance to Velcade and issues of toxicity provide significant opportunities for the development of a second generation proteasome inhibitor.

NPI-0052 is active against multiple myeloma cells that are resistant to Velcade, steroid therapy and thalidomide. The compound has also shown efficacy in animal models of myeloma, colon, pancreatic and lung cancer when administered orally or intravenously and is in Phase I clinical trials.

Nereus' preclinical program for NPI-0052 involved experts in proteasome biology, including Dr. Kenneth Anderson at the Dana Farber Cancer Institute, one of the leading clinicians responsible for the FDA approval of Velcade, and Dr. James Cusack at Massachusetts General Hospital, who described the synergistic activity of proteasome inhibitors with chemotherapy to regulate NF-kB. Additional collaborators are focused on defining the mechanisms that mediate NPI-0052-induced apoptosis in various forms of leukemia.