UBA5 Inhibitors for the Treatment of Cancer and Leishmaniasis

Cancer cells produce and break down proteins more rapidly than normal cells, and are more sensitive to changes in the regulation of processes involving proteins. The ubiquitin-proteasome system (UPS) is the main protein process that governs protein recycling in cells, and is overactive in many cancers such as leukemia and multiple myeloma. The proteasome is a large protein analogous to the recycling plant of the cell, and inhibition of the UPS with proteasome inhibitors, such as Velcade (bortezomib), results in effective cancer cell death due to the accumulation of undigested proteins. This invention involves the development novel drugs with the aim of making these cancer cells more susceptible to drug treatments, leading to the use of milder drug doses and the prevention or reduced occurrence of drug resistance.