News Release

New Jersey researchers receive national award

Grant and Award Announcement

American Chemical Society

Used snake venom as basis for successful hypertension drug

Medicinal chemists Miguel A. Ondetti of Princeton, N.J., and David W. Cushman of Lawrenceville, N.J., will be honored on August 20 by the world's largest scientific society for discovering captopril, the first of an innovative class of drugs used to control high blood pressure, heart disease and damage from heart attacks. As a team, they will be designated one of 12 Heroes of Chemistry by the American Chemical Society at its 220th national meeting in Washington, D.C.

"By the 1950s, [medical researchers] knew there was a mechanism in the body that could go berserk and raise blood pressure to very high levels," explained Ondetti. However, no one wanted to treat hypertensive patients with life-long injections. "In 1968, we decided to look into controlling this mechanism because we learned that snake venom could block it."

In 1975, after seven years of investigation, a new molecule that Ondetti and Cushman designed while at Bristol-Myers Squibb showed activity against an enzyme known to raise blood pressure. That molecule became captopril, later marketed by the pharmaceutical company in pill form as Capoten.

Over the next few years Ondetti and Cushman identified and tested venom components that thwarted a key orchestrator of the system: angiotensin converting enzyme, or ACE. But all of them broke down in the digestive tract.

In 1974, new advances led the chemists to believe that "if we hypothesize the structure of ACE, we might be able to design a small compound that could both inhibit it and be absorbed, not broken down, by digestion," said Ondetti. Previously, researchers took a trial-and-error approach to discovering new drugs.

"Their discovery of captopril represented the first example of rational drug design in the pharmaceutical industry," wrote BMS associate director Denis Ryono in nominating them for the award. "Ondetti and Cushman established a paradigm that was to spread throughout the industry." The U.S. Food and Drug Administration approved captopril for use against hypertension in 1981, and to combat heart failure and the effects of heart attack a few years later.

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The Heros of Chemistry program, started in 1996, honors industrial chemists and chemical engineers who create commercially successful products that improve the quality of life.

A nonprofit organization with a membership of 161,000 chemists and chemical engineers, the American Chemical Society publishes scientific journals and databases, convenes major research conferences, and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.


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