ACS Landmark at RTI to Commemorate Discovery of Taxol, Camptothecin
Natural Products Lab: Drs. Wall and Wani
RESEARCH TRIANGLE PARK, N.C. -- The American Chemical Society (ACS) recently announced it will commemorate the discovery of the anticancer pharmaceuticals Taxol© and camptothecin™ by Dr. Mansukh Wani and the late Dr. Monroe Wall with a National Historic Chemical Landmark. The plaque, to be presented at a commemoration event scheduled for April 23 at RTI headquarters in Research Triangle Park, will be affixed to the front of the Medicinal Chemistry Building.
National Historic Chemical Landmarks
National Historic Chemical Landmarks commemorate discoveries, products, achievements, and places that have expanded the frontiers of knowledge and advanced medicine and industry. Accordingly, RTI was selected for the landmark not only because Taxol and camptothecin have prolonged and saved the lives of hundreds of thousands of people who have cancer, but also because their discoveries have led to new modes of action to kill cancer cells and new ideas about finding and refining bioactive compounds from natural sources (see the ACS story about the discovery of camptothecin and Taxol).
"Status as a National Historic Chemical Landmark reemphasizes the seminal work of Drs. Wall and Wani in isolating and elucidating the structure of substances that have saved the lives of many people afflicted with cancer and improved the lives of many others," noted Dr. Judah Ginsberg, member of the ACS landmark program.
This ACS landmark will be the second in North Carolina; the first, near Eden, commemorates the 1892 discovery of the first manufacturing process to make calcium carbide and acetylene, which enabled advances such as synthetic processes to make rubber. In addition, the landmark will be the second established in honor of Drs. Wall and Wani's discoveries; the first was established last summer in Washington state for Taxol.
The Discovery of Taxol and Camptothecin
Drs. Wall and Wani reported the structure of Taxol, found in the Pacific yew tree Taxus brevifolia, in 1971 and the structure of camptothecin, found in the Chinese tree Camptotheca acuminata, in 1966. Other researchers identified Taxol’s unique mode of action as the stabilization of microtubule assembly, which inhibits cell division, and camptothecin’s as the inhibition of DNA topoisomerase I, which prevents DNA replication.
Today, Taxol is approved for the treatment of refractory ovarian cancer, metastatic breast and lung cancers, and Kaposi's sarcoma. First-generation analogs of camptothecin—Hycamtin and Camptosar, marketed by GlaxoSmithKline and Pharmacia, respectively—are approved for the treatment of ovarian and colon cancers. Taxol and camptothecin analogs make up one-third of the global $10-billion-per-year market for chemotherapeutic agents.
Current Natural Products Research at RTI
Although Dr. Wall passed away last summer, scientists in the Natural Products Laboratory (NPL) continue to work on several different aspects of natural products research. Today, the group is led by Dr. Wani and a new generation of investigators, including Drs. Nicholas Oberlies and David Kroll. Research areas include drug discovery and development of anticancer assays, analog development, and analysis of herbal drugs.
Drug Discovery and Anticancer Assays
In drug discovery, NPL scientists are studying several different types of organisms for bioactivity. The group's historical success in plants is still being pursued, but other life forms have been added, such as mushrooms (through an American Cancer Society grant), predator bacteria, and microscopic fungi. These sources are being tested for their ability to kill cancer cells, as well as for antimicrobial activities, including antibiotic, antifungal and anti-tuberculosis properties. In addition, Kroll, who joined NPL a year ago, is helping to further develop the testing of extracts and pure compounds for their ability to kill cancer cells, a key aspect of all drug discovery efforts.
Analog Development
A logical extension of drug discovery is the synthesis of analogs of the original natural product compound. Often, as in the case of camptothecin, the originally discovered compound has properties that are undesirable for a pharmaceutical. By creating related compounds (e.g., first-generation analogs Hycamtin and Camptosar), NPL scientists try to improve the potency while at the same time decreasing any deleterious side effects. They are now striving to create second-generation analogs of camptothecin with improved activity and reduced side effects.
Herbal Drug Analysis
Developing reference standards for herbal drugs is a growing area of research for NPL. Herbal products continue to enjoy considerable popularity in the United States, but despite this, their long history of use, and a fair amount of modern clinical data, gaps in the scientific base persist. NPL researchers are developing improved methods to standardize herbal drugs by combining their knowledge of natural products with that of other chemists and researchers at RTI. Together, they are investigating such aspects as the metabolism, efficacy, and potential contamination of herbal drugs. "Having this diverse pool of researchers and skills distinguishes our efforts in herbal drug analysis from those of similar labs," said Oberlies.
The American Chemical Society
The American Chemical Society is a self-governed individual membership organization that consists of more than 163,000 members at all degree levels and in all fields of chemistry. The organization provides a broad range of opportunities for peer interaction and career development, regardless of professional or scientific interests. The programs and activities conducted by ACS today are the products of a tradition of excellence in meeting member needs that dates from the Society's founding in 1876.
*Taxol, a word coined by Monroe E. Wall of RTI, is a registered trademark of the Bristol-Myers Squibb Company. Camptothecin is a trademark of RTI.
news@rti.org
Lisa Bistreich: 919-316-3596
Patrick Gibbons: 919-541-6136
PO Box 12194
Research Triangle Park, NC 27709-2194
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