Treat multiple myeloma and other solid cancers
Though incurable, multiple myeloma is treatable and the current treatments include steroids, chemotherapy, covalent proteasome inhibitors, immunomodulatory drugs, and stem cells transplants. UK researchers have discovered a novel pyrazole scaffold compound that targets the active site of proteasomes. The lead compound, G4-1, was also shown to be greatly effective in suppressing tumor growth in mouse xenograft models of prostate cancer. It has demonstrated to be just as effective in killing parental cells and model cell lines which has developed resistance to bortezomib or carfilzomib. As a non-covalent inhibitor which is reversible, G4-1 targets the β5 and β5i subunits of the proteasome which are located on the two different subtypes Constitutive Proteasome (CP) and Immunoproteasome (IP) respectively. These are also the key targets for the currently marketed products.
Each year, multiple myeloma occurs in approximately 10 per 100,000 around the world and in 15 per 100,000 people within the United States. It is a cancer of plasma cells due to an accumulation of abnormal plasma cells in the bone marrow. This interferes with the production of normal blood cells. Currently, the five-year survival rate is 45 percent.