Notes

Scientists seek sea squirts by the seashore

Squirt, known as Ecteinascidia turbinate, from sea bottoms around the world, a Spanish company, PharmaMar, has established an underwater farm on which the tube like creatures are being raised. - ET-743

Two years ago, Elias J. Corey, Sheldon Emery Professor of Chemistry at Harvard, managed to make the drug synthetically. He called it "the most complex molecule ever made on a commercial scale."

PharmaMar says that a harvest of about 95,000 pounds of sea squirts yields a scant 3 ounces of the drug. But it is so incredibly powerful, only 0.05 ounce is enough to treat 100 patients. According to Corey, a mere 11 pounds of the drug would satisfy world demand for about a year

Kenneth Rinehart, a chemist at the University of Illinois, discovered ET-743 (Ecteinascidia) in squirts he collected in the West Indies in the late 1980s.

In the beginning, ET-743 appeared to cause liver problems. However, this side effect "turned out to be reversible and manageable with repeated treatments," Chabner says.

Johnson & Johnson has licensed the drug for sale in the United States. However, it will take several more years to get approval in this country because the Food and Drug Administration requires Phase III trials, which compare new drugs to standard treatments in hundreds of patients.

A drug called doxorubicin is now the first line of defense against most soft-tissue cancers in the United States, but only approximately 15 percent of patients respond to it. Treatment can halt progression of the disease, but in most of these patients the cancer returns and becomes resistant to the drug

Majority of drugs used to fight cancer are most effective against tumors that have lost the ability to repair their DNA, or genetic material. ET-743, in contrast, is most active in tumors where DNA repair goes on uninterrupted. Proteins that do such repairs create breaks in the DNA strands when they cut out unwanted pieces. The sea squirt compound seems to prevent repair proteins from mending the breaks.

In theory, this combination would be a one-two punch; cisplatin would kill repair-deficient cells and ET-743 would kill cells that survive cisplatin.

To me the sea is a continual miracle.

- Whitman

Sea Squirt Discovery and Drugs

Ecteinascidia (ek-TIN-aside-in), the drug is being tested on terminally ill patients suffering with cancers of the blood vessels, tendons, muscles, and other soft tissues.

Scraping the squirts off Caribbean coral reefs in large numbers.

Elias J. Corey, winner of the 1990 Nobel Prize in chemistry, in whose laboratory the compound was first fashioned.

Ecteinascidin is so powerful that a mere 11 pounds of it should be enough to satisfy the present world demand for an entire year

Corey and Martinez have now come up with a simpler and less expensive version of Ecteinascidin called phthalascidan (THAL-aside-in).

Kenneth Rinehart discovered the drug while diving on reefs in the West Indies in the late 1980s

Ecteinascidia turbinate a sea squirt

Despite the potential of the drug, purifying it turned out to be laborious and expensive. Ten pounds of sea squirts yielded only millionths of an ounce of ecteinascidin.

Patients are responding positively to exceedingly small doses of ecteinascidin.

A course of treatment consists of nine injections or a total of less than 14 milligrams of the drug. (A single aspirin contains 325 milligrams.)

a drug that is structurally simpler, easier to make, and comparable to ecteinascidin in potency – phthalascidin

Both drugs work by interacting with DNA and an unknown protein in cancer cells. The drugs do not kill tumor cells; rather, they prevent them from reproducing and growing.

Endostatin - works by blocking the development of blood vessels that bring oxygen and sustaining nutrients to tumors. we could use it together with ecteinascidin or phthalascidin