Ann Arbor chemist wins national award for drug discovery

Bruce D. Roth of Ann Arbor, Mich., will be honored March 25 by the world's largest scientific society for inventing and helping develop the molecule that would become Lipitor, the most commonly prescribed drug to lower cholesterol. He will receive the 2003 ACS Award for Creative Invention from the American Chemical Society at its national meeting in New Orleans.

"With 20-20 hindsight everything seems obvious, but in 1982 it wasn't clear whether lowering plasma cholesterol would have a benefit or that we could do it safely," said Roth, who is vice president of chemistry at Pfizer Global Research and Development. That was the year Roth joined the company (then Parke-Davis) and began work on a class of compounds, originally extracted from fungi, that held both promise and challenge in lowering cholesterol, averting heart disease and premature death.

The highly complex fungal products, called statins, blocked cholesterol synthesis at a key step. Roth's challenge was to make a molecule that acted the same as statins but was straightforward to assemble. He met that challenge in 1985.

Between his discovery and Lipitor's market debut in 1997, however, were 12 years of more work: first, to make the drug in pure form, then to scale up from laboratory to cost-efficient manufacturing. Only then came the decision to begin human clinical trials. Along the way were entire teams of chemists and others who contributed to Lipitor's development, Roth noted.

The trick to Roth's structure was first learning what parts of statins were necessary to work and in what fashion. Then he studied which he could replace with simpler components. The part of Lipitor that anchors the drug in place, for example, went from a highly complicated structure to one that used equally bulky but readily available molecular rings.

Pfizer says the drug has since logged more than 36-million patient years of experience and some 400 clinical trials involving more

Contact: Allison Byrum
American Chemical Society

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