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© 2005 Oxford University Press
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Missing the Target: Ubiquitin Ligase Drugs Stall
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These should be the best of times for drug companies targeting the cell's garbage disposal system. The 2004 chemistry Nobel Prize affirmed for the world the importance of the system, the ubiquitin–proteasome pathway, in human biology and cancer. The proteasome inhibitor Velcade (bortezomib), approved by the U.S. Food and Drug Administration in May 2003 for treating multiple myeloma, heralded an entirely new class of cancer drugs. In particular, E3 ubiquitin ligases, which catalyze the transfer of ubiquitin chains to proteins, marking them for degradation in the proteasome, offered seemingly ideal drug targets.
"Because each E3 is responsible for the destruction of a small number of proteins, specific inhibitors of E3s should be highly specific drugs with few side effects," J. Wade Harper, Ph.D., of Harvard University, wrote in Scientific American 4 years ago.
That optimism was premature. No known E3 inhibitor has yet reached the clinic or even appears to
Perils of the Unknown
Taking p53 to New Levels
Easier Targets, Messier Drugs?
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