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Sponsored by the Schering-Plough Research Institute
Choung U. Kim, vice president of chemistry at Gilead Sciences, is described by one of his colleagues as "a gifted and dedicated medicinal chemist" and "one of the best in the pharmaceutical industry." He is being honored for discovering Tamiflu, an oral drug that is widely used to treat and prevent influenza. The drug is also being stockpiled by countries around the world in preparation for an avian flu pandemic.
Kim says he first became interested in chemistry while taking an undergraduate course that involved organic synthesis experiments at the University of Tokyo, where he earned bachelor's and master's degrees. He earned a Ph.D. in organic chemistry from the University of Oregon and further developed his organic synthesis skills as a postdoc with Satoru Masamune of the University of Alberta, in British Columbia, and with Elias J. Corey of Harvard University. Kim then switched gears in 1973 and began a career with the pharmaceutical industry, starting at Bristol-Myers Laboratories (now Bristol-Myers Squibb) and then joining Gilead in 1994.
With more than 30 years of industrial experience, Kim has discovered numerous drug candidates, including antiviral, antimicrobial, antifungal, and anticancer agents. But the rational drug design of Tamiflu is undoubtedly his most significant research accomplishment, he says.
Kim discovered Tamiflu by studying sialic acid derivatives that inhibit the enzyme neuraminidase on the surface of influenza viral particles. Without the enzyme, the virus cannot replicate and infect new host cells. He proposed that the chemical stability of the sialic acid derivatives would be enhanced if they contained a carbocyclic ring instead of a dihydropyran ring.
With the help of X-ray crystallography, Kim confirmed that a carbocyclic ring analog could bind to neuraminidase. He also observed a hydrophobic pocket in the active site of the enzyme that had been previously undiscovered. He latched onto that observation and eventually exploited it, developing new analogs that were both bioavailable and maintained their antiviral activity. That work led to the discovery of Tamiflu, a compound that contains three contiguous chiral centers on a cyclohexene ring. The method that Kim developed to synthesize Tamiflu is still widely used today for commercial production of the drug.
"The key to his success is his overwhelming knowledge of synthetic chemistry, extensive experience in drug discovery, unparalleled creativity, and exceptional drive to make the difference," says one of his colleagues. Kim is "a confident, yet humble, scientific leader that numerous young scientists respect and seek to emulate."
When Kim is not discovering new drug candidates in the lab, he can be found hiking near his home in the Bay area of northern California or sitting for Zen meditation. He says the award means a lot to him, not because Tamiflu has made his company a lot of money but because of its benefits to society. "Everyone in drug research wants to make new discoveries to help mankind. As excited as I am that we discovered Tamiflu, I am much more grateful that it has helped countless numbers of people around the world," he says.
Kim will present the award address before the Division of Medicinal Chemistry.
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