Plants have traditionally been one of man's richest sources of biologically active materials; over 25% of all prescriptions dispensed in the U.S. contain a plant derived active principle. In collaboration with the University of Illinois at Chicago and Research Triangle Institute, Bristol-Myers Squibb plans to identify, isolate and characterize novel plant derived anticancer agents. Bristol-Myers Squibb Pharmaceutical Research Institute is a part of one of the largest pharmaceutical companies in the world with a strong commitment and resources dedicated to natural products screening. With respect to the NCNPDDG in question, we plan to carry out the following specific aims. 1. To assay ca. 500 plant samples per year for cytotoxicity, interaction with specific oncogenes, enzymes and proteins of DNA metabolism. 2. To assist in selecting and prioritizing the most biologically significant leads. 3 To support bioassay-guided fractionation of the active constituents. 4. To participate in the isolation and structure elucidation of the active constituents. 5. To obtain sufficient amounts of active compounds, by extraction and purification or by partial or total synthesis, depending upon the complexity of the molecule in question. 6. To profile in vitro and in vivo the biological properties of lead compounds obtained from this program. 7. To carry out the large-scale isolation and/or synthesis and the preclinical drug development of lead candidates. Bristol-Myers Squibb has an outstanding track record in accomplishing this type of aim, having successfully brought to clinical trials over five anticancer agents in the past six to seven years and having successfully solved the taxol supply problem.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19CA052956-09S2
Application #
6296014
Study Section
Project Start
1998-09-01
Project End
1999-08-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Li, Jie; Pan, Li; Deng, Ye et al. (2013) Sphenostylisins A-K: bioactive modified isoflavonoid constituents of the root bark of Sphenostylis marginata ssp. erecta. J Org Chem 78:10166-77
Ren, Yulin; Acuña, Ulyana Muñoz; Jiménez, Francisco et al. (2012) Cytotoxic and NF-?B inhibitory sesquiterpene lactones from Piptocoma rufescens. Tetrahedron 68:2671-2678
Pan, Li; Chai, Hee-Byung; Kinghorn, Alan Douglas (2012) Discovery of new anticancer agents from higher plants. Front Biosci (Schol Ed) 4:142-56
Pan, Li; Yong, Yeonjoong; Deng, Ye et al. (2012) Isolation, structure elucidation, and biological evaluation of 16,23-epoxycucurbitacin constituents from Eleaocarpus chinensis. J Nat Prod 75:444-52
Ren, Yulin; Matthew, Susan; Lantvit, Daniel D et al. (2011) Cytotoxic and NF-?B inhibitory constituents of the stems of Cratoxylum cochinchinense and their semisynthetic analogues. J Nat Prod 74:1117-25
Kinghorn, A Douglas; Pan, Li; Fletcher, Joshua N et al. (2011) The relevance of higher plants in lead compound discovery programs. J Nat Prod 74:1539-55
Deng, Ye; Chin, Young-Won; Chai, Hee-Byung et al. (2011) Phytochemical and Bioactivity Studies on Constituents of the Leaves of Vitex Quinata. Phytochem Lett 4:213-217
Gupta, Sneha V; Sass, Ellen J; Davis, Melanie E et al. (2011) Resistance to the translation initiation inhibitor silvestrol is mediated by ABCB1/P-glycoprotein overexpression in acute lymphoblastic leukemia cells. AAPS J 13:357-64
Pan, Li; Chai, Heebyung; Kinghorn, A Douglas (2010) The continuing search for antitumor agents from higher plants. Phytochem Lett 3:1-8
Pan, Li; Lantvit, Daniel D; Riswan, Soedarsono et al. (2010) Bioactivity-guided isolation of cytotoxic sesquiterpenes of Rolandra fruticosa. Phytochemistry 71:635-40

Showing the most recent 10 out of 84 publications