[I would like to understand the relationship among Endothelin-A antagonists and the separate indications pursued by Abbott (cancer) and TXB/ICOS (cardio/vascular).
From WSJ Online: public.wsj.com
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So doctors have theorized that any drug blocking this process -- an endothelin "antagonist" -- could fight high blood pressure and congestive heart failure. But, it turns out, endothelin also is produced by prostate cancer cells and might play a role in the metastasizing of the illness. Hence, Abbott targeted the drug at that disease, and a Japanese company, Yamanouchi Pharmaceutical Co., also has been exploring the idea.
Because atrasentan doesn't interfere with the production of testosterone, as do Lupron and Zoladex, it doesn't produce unwanted sexual side effects in men, such as loss of sex drive and even growing breasts.
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The scientific story leading to Abbott's new approach dates to 1988. Masashi Yanagisawa, a Ph.D. student at the time, stunned the medical world with his doctoral thesis. Published on April Fool's Day, the paper by the unknown Japanese researcher was so startling that many thought at first it was a prank.
Printed in the scientific journal Nature, the paper by Dr. Yanagisawa and colleagues described their discovery of endothelin. They went on to detail the protein's role in constricting blood vessels and human disease. It was more potent in that function than the twin hormones angiotensin and norepinephrine, the most powerful "vasoconstrictors" previously known, the authors wrote.
"That caught the imagination of a lot of people in the cardiovascular field," says Terry Opgenorth, Abbott's divisional vice president of metabolic disease research. Soon, Abbott, like many U.S. and European drug companies, had launched an endothelin-based search for a new cardiovascular drug.
Dr. Nelson, a research fellow in the mid-1990s at Johns Hopkins Hospital in Baltimore, became intrigued with endothelin as well, but for different reasons. In the mid-1990s, he was supposed to be working on gene therapy, or inserting genes into human cells to treat cancers. One way of checking to see if genes were being successfully inserted in the cells was to plant a certain gene in the cell that effectively gave it a blue hue.
"Here I am trying to turn cells blue, and I'm no closer to curing prostate cancer," he recalls. "I figured I had better come up with something else fast, so I snuck off and did prostate-cancer work secretly."
By 1995, he produced his own groundbreaking discovery: prostate-cancer cells secrete endothelin, which might play a role in the metastasis of prostate cancer in bones and elsewhere. He described his finding that year in Toronto at a meeting of the American Association of Cancer Research.
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