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Nobel Laureate Creates Potent Anticancer Weapons

Date:
April 14, 2000
Source:
American Chemical Society
Summary:
Two anticancer drugs, each estimated to be at least 100 times more powerful than the potent anticancer medication Taxol®, have been synthesized by a renowned Harvard University chemist. The findings are reported in the current (April 6) print edition of Organic Letters, published by the American Chemical Society.

Synthesizes new drugs more powerful than Taxol®

Two anticancer drugs, each estimated to be at least 100 times more powerful than the potent anticancer medication Taxol®, have been synthesized by a renowned Harvard University chemist. The findings are reported in the current (April 6) print edition of Organic Letters, published by the American Chemical Society, the world's largest scientific society.

Elias J. Corey, Ph.D., winner of the 1990 Nobel Prize for chemistry, has developed a new and better way to make ecteinascidin (pronounced ek-TIN-aside-in), a drug first produced in 1996 but little used until now because it is so difficult to make. The new method should speed and simplify mass production of the antitumor substance, potentially making the drug more available to patients suffering from soft-tissue sarcomas like cancers of the muscles, tendons and blood vessels. Ecteinascidin is likely the most complicated molecule ever to be made on a commercial scale, according to Corey.

He referred to the compound as "approximately two orders of magnitude stronger (than Taxol®) in inhibiting tumor cell growth. This is another example of how synthetic chemistry contributes to medicine." (Paclitaxel, known commercially as Taxol®, is used to treat ovarian and breast cancers, and has shown promising results in studies using it to treat Alzheimer's disease, multiple sclerosis and polycystic kidney disease, among others.)

Ecteinascidin and a simpler, easier to make form called phthalascidin (pronounced THAL-aside-in), act differently than Taxol® and every other cancer cell treatment. They have a unique molecular interaction 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.

Ecteinascidin is currently undergoing phase two human testing at Massachusetts General Hospital in Boston, the Memorial Sloan-Kettering Cancer Center in New York and M.D. Anderson Cancer Center in Houston. The human trials are expected to finish 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.

The manufacturer that owns the rights to the drug, Pharma Mar, 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.

The natural form of the drug is found in a reef-living animal called Ecteinascidia turbinate, found in the West Indies. It was originally discovered approximately 12 years ago by a former colleague of Corey's from the University of Illinois, an avid diver. After discovering the agent in the finger-shaped appendages of the tiny animal, the colleague called it the most powerful anti-cancer drug he had ever seen. Previous attempts at chemically creating sufficient amounts of the substance failed, however.

Because synthetic ecteinascidin and phthalascidin are so strong, as little as 14 milligrams (mg) can last a patient up to six months. At the current dosage during the trial phase, patients are injected with 1.5 mg a week for three weeks. At that rate, approximately five kilograms, or 11 pounds, of the drug could supply the world demand for an entire year, Corey estimated.

"It's especially effective against soft-tissue sarcoma," Corey said. "There hasn't been effective chemotherapy for sarcoma. That's been the most striking result so far."

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.

"I love to discover new chemistry and to develop syntheses of new medically useful compounds," Corey said. "This type of research is driven by the great power of modern chemistry. I hope that ecteinascidin and phthalascidin will be useful as life-saving drugs, but it will be another five years before we know for certain."


Story Source:

The above story is based on materials provided by American Chemical Society. Note: Materials may be edited for content and length.


Cite This Page:

American Chemical Society. "Nobel Laureate Creates Potent Anticancer Weapons." ScienceDaily. ScienceDaily, 14 April 2000. <www.sciencedaily.com/releases/2000/04/000410084213.htm>.
American Chemical Society. (2000, April 14). Nobel Laureate Creates Potent Anticancer Weapons. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2000/04/000410084213.htm
American Chemical Society. "Nobel Laureate Creates Potent Anticancer Weapons." ScienceDaily. www.sciencedaily.com/releases/2000/04/000410084213.htm (accessed September 17, 2014).

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