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Potent Anti-Cancer Drugs Synthesized
4/20/2000  Two anticancer drugs, each estimated to be at least 100 times more powerful than Taxol, have been synthesized by renowned Harvard University (Cambridge, MA) chemist and Nobel Laureate, Elias Corey. The findings are reported in the current (April 6) print edition of Organic Letters, published by the American Chemical Society.
Corey, winner of the 1990 Nobel Prize for chemistry, developed a new way to make ecteinascidin, the most complicated molecule ever to be made on a commercial scale. First produced in 1996, it has been little used until now because it is so difficult to make.

Ecteinascidin, the natural form of which is made by the reef-dwelling marine organism Ecteinascidia turbinata, is among the most powerful anti-cancer drugs ever found-two orders of magnitude stronger than Taxol, for example, in inhibiting tumor cell growth. However, it had proven difficult to create chemically in sufficient amounts for testing.
Ecteinascidin and a simpler, easier-to-make form called phthalascidin interact uniquely with DNA and with a currently unknown protein associated with the DNA, Corey said. Laboratory studies, combined with research conducted on ecteinascidin through the National Institutes of Health, have found the drug prevents tumor cell division without killing off the cells, unlike chemotherapy.
Phase II human trials, currently underway at Massachusetts General Hospital in Boston, the Memorial Sloan-Kettering Cancer Center in New York, and M.D. Anderson Cancer Center in Houston, are expected to be finished by the end of the year 2000, and phase three testing will begin soon after. Phthalascidin is equally effective clinically, and more stable, but has not yet begun human trials.
An exciting feature of these drugs is their effectiveness against sarcomas, which are notoriously difficult to treat. Corey believes that the drug's unique mechanism of action may explain why it is effective against sarcoma.
"The drug has a different mechanism of action from every one of the chemotherapeutic agents now used and the way we know this, is that... tumor (cells) that have developed resistance to known and standard chemotherapeutic agents... are still sensitive to ecteinascidin or phthalascidin," Corey said.

Pharma Mar, a Spanish biotech company that focuses on developing drugs from marine life, owns the rights to these drugs, and will seek "fast-track" approval of the medication through the U.S. Food and Drug Administration. Barring unforeseen complications, the drug could be on the market in 2002.

Reporting the results after two years of testing, research and study, Corey and graduate student Eduardo Martinez created more than 100 other derivatives of the drug, none more powerful than the two synthesized molecules.

For more information: Elias J Corey, Department of Chemistry, Harvard University, Cambridge, MA 02138. Tel: 617-495-4033. Fax: 617-495-0376. Email: corey@chemistry.harvard.edu
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