Tumor-starving drug's mechanism clarified

Abstract

New details about the way a key anticancer drug interacts with its human target protein have been revealed though independent studies by two research groups. The studies could aid the structure-based design of agents with improved activity and lower toxicity and could lead to a better fundamental understanding of the drug's effects in the body. The drug, TNP-470, is an analog of the fungal natural product fumagillin. Both compounds fight cancer by curbing angiogenesis, the growth of the new blood vessels that tumors need to sustain themselves and spread. The agents act by inhibiting methionine aminopeptidase-2 (MetAP-2), an enzyme that plays a key role in protein synthesis. In 1992, TNP-470 became the first anti-angiogenesis drug to enter the clinic as an anticancer agent. It is currendy in Phase II trials sponsored by TAP Pharmaceuticals, Deerfield, Ill. However, it is toxic to some degree and breaks down quickly in the body, so drug researchers are interested ...