Back to Nature: Rethinking Natural Products as Sources of Drug Leads
Posted February 29, 2008
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Overview
Although pharmaceutical companies have highly invested in combinatorial chemistry and high-throughput screening, such approaches have not met initial expectations in their ability to identify new drug candidates. Natural products, which provide qualitatively different chemicals than purely synthetic compounds, could offer a more cost-effective strategy for discovering new drugs.
A January 22, 2008, meeting at the Academy explored the use of natural products as sources for new drugs. High-throughput screening methods and rational drug design with natural products as a starting point has already yielded several druggable lead compounds.
Journal Articles
Ronald Quinn
McArdle BM, Campitelli MR, Quinn RJ. 2006. A common protein fold topology shared by flavonoid biosynthetic enzymes and therapeutic targets. J. Nat. Prod. 69: 14-17.
McArdle BM, Quinn RJ. 2007. Identification of protein fold topology shared between different folds inhibited by natural products. Chembiochem. 8: 788-798.
Mitchell JK, Pitcher D, McArdle BM, et al. 2007. Identifying common metalloprotease inhibitors by protein fold types using Fourier Transform Mass Spectrometry. Bioorg. Med. Chem. Lett. 17: 6521-6524.
Guy Carter
Ruan B, Pong K, Jow F, et al. 2008. Binding of rapamycin analogs to calcium channels and FKBP52 contributes to their neuroprotective activities. Proc. Natl. Acad. Sci. USA 105: 33-38.
Ritacco FV, Graziani EI, Summers MY, et al. 2005. Production of novel rapamycin analogs by precursor-directed biosynthesis. Appl. and Environ. Microbiol. 71: 1971-1976. Full Text
Ray Lam
Lam KS. 2007. New aspects of natural products in drug discovery. Trends Microbiol. 15: 279-289.
Tseung G, Lam KS. 2008. A low-sodium-salt formulation for the fermentation of salinosporamides by Salinispora tropica strain NPS21184. Appl. Microbiol. Biotechnol. [Epub ahead of print]
Tsueng G, Teisan S, Lam KS. 2008. Defined salt formulations for the growth of Salinispora tropica strain NPS21184 and the production of salinosporamide A (NPI-0052) and related analogs. Appl. Microbiol. Biotechnol. [Epub ahead of print]
Sheo Singh
Jayasuriya H, Herath KB, Zhang C, et al. 2007. Isolation and structure of platencin: a FabH and FabF dual inhibitor with potent broad-spectrum antibiotic activity. Angew. Chem. Int. Ed. 46: 4684-4688.
Singh SB, Jayasuriya H, Ondeyka H, et al. 2006. Isolation, structure, and absolute stereochemistry of platensimycin, a broad spectrum antibiotic discovered using an antisense differential sensitivity strategy. J. Am. Chem. Soc. 128, 11916-11920.
Singh SB, Pelaez F. 2008. Biodiversity, chemical diversity and drug discovery. Prog. Drug Res. 65: 141, 143-174.
Wang J, Kodali S, Lee SH, et al. 2007. Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties. Proc. Natl. Acad. Sci. USA 104: 7612-7616. Full Text
Wang J, Soisson SM, Young K, et al. 2006. Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature 441 358-361.
Arnold Demain
Demain AL, Adrio JL. 2008. Contributions of microorganisms to industrial biology. Mol. Biotechnol. 38: 41-55.
Demain AL. 2006. From natural products discovery to commercialization: a success story. J. Ind. Microbiol. Biotechnol. 33: 486-495.
Speakers
Takushi Kaneko, PhD
Global Alliance for TB Drug Development
e-mail | web site | publications
Takushi Kaneko is a project leader of research at the Global Alliance for TB Drug Development, where he is responsible for evaluating discovery projects for inclusion in the TB Alliance portfolio and overseeing current drug discovery projects. Prior to joining the TB Alliance in October 2007, he was a research fellow in the antibacterial drug discovery team and manager of the natural product discovery group at Pfizer Global Research and Development Division in Groton, CT. He holds a PhD in organic chemistry from the University of Michigan, and trained as a postdoctoral fellow at Harvard.
Ronald J. Quinn, PhD
Griffith University
e-mail | web site | publications
Ronald Quinn received his PhD from the University of New South Wales, Australia, and then did postdoctoral work at Arizona State University, the University of Hawaii, and Australian National University. He then joined the Roche Research Institute, where he worked on marine-derived pharmaceutical compounds. Since 1994, he has been a full professor at Griffiths University in Australia.
Guy Carter, PhD
Wyeth Research
e-mail | publications
Guy Carter is the assistant vice president for chemical sciences and screening at Wyeth Research, and heads the natural products discovery operation for the company. He holds an undergraduate degree from Lehigh University, and a PhD from the University of Wisconsin.
Ray Lam, PhD
Nereus Pharmaceuticals
e-mail | web site | publications
After earning his PhD in biochemistry at the University of Calgary, Ray Lam became a research scientist at the National Research Council of Canada, then joined Bristol-Myers Squibb, where he climbed through the ranks as a researcher for 16 years. He is now vice president of microbiology and anti-infective discovery at Nereus Pharmaceuticals.
Sheo Singh, PhD
Merck Research Labs
e-mail | web site | publications
Currently the director and head of natural products chemistry at Merck Research Labs, Sheo Singh earned his PhD in 1981, then pursued postdoctoral research at the University of Glasgow and Arizona State University. He joined Merck in the late 1980s. In 2006, he also received an honorary doctorate from Stevens Institute of Technology.
Arnold L. Demain, PhD
Drew University
e-mail | web site | publications
One of the world's leading industrial microbiologists, Arnold Demain began his career at Merck, where he founded the department of fermentation microbiology. He then moved to the Massachusetts Institute of Technology, where he was a professor of industrial microbiology for over 30 years. He is a member of the National Academy of Sciences, and a Fellow in the Charles A. Dana Research Institute for Scientists Emeriti (RISE) at Drew University.
Alan Dove
Alan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism, and blogs at http://dovdox.com.