Researchers report new finding on anticancer agent

by William G. Gilroy

A recent finding by researchers from the University of Notre Dame’s Walther Cancer Research Center may assist in the design of new anticancer agents. The development was announced last month in the Journal of the American Chemical Society.p. Richard E. Taylor, associate professor of chemistry and biochemistry, and Yue Chen, a chemistry and biochemistry graduate student, designed analogs, or variants, of epothilones, which are naturally occurring anticancer compounds. Epothilones mimic all the biological effects of the anticancer agent Taxol, which currently is marketed by Bristol-Myers Squibb. However, preclinical tests on epothilones have shown that they may be even more powerful than Taxol. They are slightly soluble in water, while Taxol is highly insoluble, which should make drug formulation easier. Epothilones also are effective against some cancer cells that have developed resistance, which is an increasing concern with Taxol. Several variants of epothilones currently are in clinical trials.p. The Taylor group made analogs of epothilones to probe the importance of conformation, or the preferred shape of a flexible molecule, on their biological activity. One set of conformationally restricted analogs had activities similar to the corresponding natural epothilones, but a second set was completely inactive. The biological analyses were carried out through collaboration with Kosan Biosciences of Hayward, Calif.p. “Insights gained through this work pave the way for the identification of additional novel epothilone analogs with increased potency and improved properties,” said David C. Myles, executive director of chemistry at Kosan. The researchers hope to use the strategy of conformational restriction to help design epothilone analogs with increased potency and improved properties.p. The academic-industrial collaboration is continuing and Kosan and Notre Dame are pursuing patents. On Jan. 10, Notre Dame and Kosan finalized a sponsored research agreement to support the team’s continued research in Taylor’s laboratory in this area and completed negotiations for an exclusive license agreement for potential commercialization of these anticancer compounds. Michael Edwards, director of technology transfer at Notre Dame, was instrumental in these negotiations.p. The National Institutes of Health also supported the research.p.

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