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Camptothecin and Taxol: Discovery to Clinic—Thirteenth Bruce F. Cain Memorial Award Lecture¹

Research Triangle Institute, Research Triangle Park, North Carolina 27709-2194

Camptothecin and taxol are secondary metabolites found, respectively, in the wood bark of Camptotheca acuminata, a native of China, and Taxus brevifolia, found in the northwest Pacific coastal region of the United States. The compounds were isolated guided by bioassay on various extracts and chromatographic fractions. Their unique and hitherto unknown structures were elucidated by nuclear magnetic resonance, mass spectrometry, and X-ray analysis. Both compounds have unique mechanisms of antitumor activity; camptothecin uniquely inhibits an enzyme, topoisomerase I, involved in DNA replication. Taxol binds to a protein, tubulin, thus inhibiting cell division. Taxol has been called the best new anticancer agent developed from natural products, showing particular efficacy against ovarian cancer. Camptothecin and analogues singly or combined with cisplatin show efficacy against solid tumors, breast, lung, and colorectal, which hitherto have been unaffected by most cancer chemotherapeutic agents.

¹ Presented at the 85th Annual Meeting of the American Association for Cancer Research, April 13, 1994, San Francisco, CA. The discovery, isolation, and structure elucidation of campothecin and taxol were carried out under Contract SA-43-ph-4322.

² To whom requests for reprints should be addressed, at Chemistry and Life Sciences, Research Triangle Institute, P.O. Box 12194, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194.

Received 12/ 7/94. Accepted 12/12/94.

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