E. B. Hershberg Award for Important Discoveries in Medicinally Active Substances | Chemical & Engineering News
Volume 85 Issue 4 | p. 47 | Awards
Issue Date: January 22, 2007

E. B. Hershberg Award for Important Discoveries in Medicinally Active Substances

Department: ACS News
Credit: Courtesy of John A. Katzenellenbogen
Credit: Courtesy of John A. Katzenellenbogen

Sponsored by Schering-Plough

John A. Katzenellenbogen, Swanlund Professor of Chemistry at the University of Illinois, Urbana-Champaign, is being honored for his pioneering research at the interfaces of chemistry, biology, physiology, and medicine that has illuminated the molecular aspects of estrogen action. In addition, "he has expanded the chemical universe of estrogens and was the first to exploit the estrogen receptor for the in vivo imaging of tumors in humans," says Scott E. Denmark, professor of chemistry at the University of Illinois.

Early in his career, Katzenellenbogen used his synthetic skills to investigate the interaction of small-molecule ligands with hormone receptors. By arming a ligand with a chemically reactive component that would tag the estrogen receptor, he developed [3H]tamoxifen aziridine, a reactive analog of the antiestrogen tamoxifen that attaches to the estrogen receptor covalently and labels it stoichiometrically, even in unpurified cell extracts. This reagent was then used to determine the size, stability, and cellular turnover of the estrogen receptor. "This work represents one of the first examples of the use of affinity labeling to characterize a receptor in unfractionated cellular systems," Denmark says.

Next, Katzenellenbogen devised estrogens radiolabeled with gamma- or positron-emitting radionuclides, which could be used, along with imaging techniques, to provide information on estrogen receptor levels in breast tumors. He was the first to image breast tumors and breast-tumor metastases on the basis of their estrogen receptor content. These images provide information that can be used to predict patient response to hormone therapy.

Katzenellenbogen has also invented new receptor-based reagents that act as novel sensors for assessing the activity of new pharmaceuticals, and he has devised a set of compounds to selectively regulate estrogen receptors alpha and beta. "He applied the most sophisticated capabilities in organic synthesis to problems of pressing medical interest," says Samuel J. Danishefsky, director of the Laboratory for Bioorganic Chemistry at Sloan-Kettering Institute.

Born in 1944, Katzenellenbogen received his bachelor's (1966), master's (1967), and Ph.D. (1969) degrees in chemistry from Harvard University, where he worked with E. J. Corey, professor in the department of chemistry and chemical biology. He joined the chemistry faculty at the University of Illinois in 1969 and became a full professor there in 1979.

Katzenellenbogen is author or coauthor of more than 430 research publications and holds six patents. He has received numerous awards and honors, including the Aebersold Award from the Society of Nuclear Medicine in 1995, the Greep Award from the Endocrine Society in 2006, and the Cope Scholar Award from ACS in 1999. He is a fellow of the American Academy of Arts & Sciences and serves on the editorial boards of many chemical and medical journals, including Molecular Endocrinology and the Journal of Nuclear Medicine.

In recent work, "we are pushing imaging in breast and prostate cancer," Katzenellenbogen says. "It has a chance of becoming mainstream in medicine, and the pharmaceutical industry is starting to use imaging not only for developing drugs but also to guide in the selection of targeted therapy."

Katzenellenbogen's research has benefited greatly from collaboration with his wife, Benita S. Katzenellenbogen, who is a professor of physiology and cell biology at the University of Illinois. "The two of us together are like an academic pharmaceutical company. I develop compounds or probes, and she tests them in biological systems," he says.

The award address will be presented before the Division of Medicinal Chemistry.

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