National Cancer Institute natural products

Camptothecin was discovered as an active anticancer drug isolated from the bark of Camptotheca acuminata. The anticancer activity of camptothecin was discovered in the 1960s by the National Cancer Institute (NCI) as part of a systematic effort to screen for novel anticancer agents derived from natural products. Monroe Wall and Mansuhk Wani identified the chemical structure of camptothecin. They also identified the chemical structure of taxol, again under the auspices of the NCI. Susan Hoiwitz was contracted by the NCI to elucidate the anticancer mechanisms of camptothecin. She found in the early 1970s that camptothecin induced DNA breaks and attested DNA and RNA synthesis. However, it is approximately 12 years later, only after DNA topo-isomerase I (Topi) had been identified in human cells, that Leroy Liu and his coworkers found that Topi was the cellular target of camptothecin [reviewed in [1]. 

Cragg GM, BoydM. (1996) Drug discovery and development at the National Cancer Institute The role of natural products of plant origin. In Balick MJ, Elisabetsky E, Laird SA. (eds). Medicinal Plant Resources of the Tropical Forest, pp. 101-136, Columbia University Press, New York. 

I would like to express my sincere thanks and deep sense of gratitude to Dr. David J. Newman, Chief, Natural Products Branch, National Cancer Institute, USA for his keen interest in the manuscript. 

Perhaps the most exciting story about an anticancer agent derived from a natural product is that of Taxol . That story begins in 1958, when the National Cancer Institute began a program to screen natural products for substances that might have anticancer activity. The... 

Taxol has had a most unusual clinical development history. As with many natural products that have been discovered to provide therapeutic benefit to humans, it was the extract of a plant that provided the first hint of the oncological potential of this product. Natural product chemists typically subject purified plant extracts to screening for therapeuhc achvity. In 1963, an extract of the bark of the Pacific yew tree (Taxus brevifolia (Figure 7.2) showed anti-tumor activity. This early work was done by Monroe Wall and Monsukh Wani of the Research Triangle Institute (RTI) under the auspices of the National Cancer Institute (NCI) [3]. 

Antiviral agents (qv) (15—17) are used in attempts to combat the devastating effect of HIV on the immune system. As of this writing there are three principal approaches to the treatment of AIDS (/) use of anti-HIV agents to destroy the virus or control its growth the National Cancer Institute (NCI) encourages submission of synthetic and characterized natural products for anti-HIV screening (18) (2) immunotherapy to restore impaired immune functions and (3) treatment of specific opportunistic infections or tumors. 

The increasing problem of cancer in the developed world, it now being second only to cardiovascular disease as a cause of death, has motivated the extensive growth of cancer research in recent years. Mass screening programs of natural products and synthetic compounds by the National Cancer Institute of the USA have identified the quinone moiety as a pharmacophore that commonly affords cytotoxic activity [159]. 

The highly enantioselective allylation method developed by Corey was utilized iteratively during the total synthesis of phorboxazole A (13), a natural product that exhibits unprecedented cytostatic activity against all 60 cell lines of the National Cancer Institute human cancer test panel36 (Scheme 3.Iff). The... 

Academic institutions are assembling both synthetic libraries and natural product repositories. The National Cancer Institute (NCI) operates a well-received resource providing natural product extracts, mostly from marine sources (http //www.dtp.nci.nih.gov/branches/npb/repository.html). 

The discovery of Taxol is a fruit of a National Cancer Institute (NCI)-sponsored project on identification of antitumor agents from natural resources. Bioassay-guided fractionation led to the isolation of this unique compound from Taxus bre-vifolia (pacific yew). Wani et al. also identified another famous antitumor natural product camptothecin. Unlike camptothecin, which was abandoned in the phase of clinical trial because of its severe toxicity, Taxol was almost discarded at the preliminary phase because it only exhibited moderate in vitro activity toward P388, a murine leukemia cell line that was used in the standard evaluation system by NCI researchers at that time. However, it was rescued by a subsequent finding of its strong and selective antitumor activities toward several solid tumors, and more... 

Drug and biological databases BioScreen NP and SC—about 52,000 structures including natural products, Pomona College Medchem—36,000 structures with measured LogP, National Cancer Institute—... 

NATURAL PRODUCTS DRUG DISCOVERY AT THE NATIONAL CANCER INSTITUTE. PAST ACHIEVEMENTS AND NEW DIRECTIONS FOR THE NEW MILLENNIUM... 

National Cancer Institute, drug screening protocol of, 392-394. 393f Natural products, cumbinaiuriul synthesis of. 47-48. 47f... 

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