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Signal-transduction cascades as targets for therapeutic intervention by natural products
Abstract
Many bacteria and fungi produce natural products that are toxic to other microorganisms and have a variety of physiological effects in animals. Recent studies have revealed that, in several cases, the targets of these agents are components of conserved signal-transduction cascades. This article looks at the mechanisms of action of five natural products--the immunosuppressants cyclosporin A, FK506 and rapamycin, and the antiproliferative agents wortmannin and geldanamycin. These mechanisms reveal the importance of signal-transduction cascades as targets for therapeutic intervention and the enormous utility of studies of natural-product action in simple model genetic systems.
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“Geldanamycin is a natural fermentation product of the benzoquinone ansamycin and inhibits the heat shock protein HSP90 [220], as well show cytotoxic effect against HeLa cells [221].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [220]
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Metadata
- Authors
- Cardenas, M. E., Sanfridson, A., Cutler, N. S., & Heitman, J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Heitman, Joseph
- Venue
- Trends in Biotechnology
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 16
- Issue
- 10
- Pages
- 427-433
- ISSN
- 0167-7799 (ISSN-L)
- OpenAlex
- W1968232511
- Cited by
- 101
- References
- 72
- Citations by year
- 2023: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 1 · 2014: 7 · 2013: 3 · 2012: 1
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ai041937-03, 5k01ca077075-04)
- National Cancer Institute (KO1 CA77075)
- National Institute of Allergy and Infectious Diseases (AI 39115, AI41937)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- signaling pathways, natural products, microbial secondary metabolites, cyclosporine, FK506, rapamycin, wortmannin, geldanamycin, immunosuppressants, antiproliferative agents, mechanism of action, target-based drug discovery
- MeSH terms
- Wortmannin, Androstadienes, Animals, Cell Cycle, Enzyme Inhibitors, Fungi, Humans, Immunosuppressive Agents, Quinones, Protein Biosynthesis, Signal Transduction, Benzoquinones, Tacrolimus, Cyclosporine, Apoptosis, HSP90 Heat-Shock Proteins, Calcineurin, Sirolimus, Lactams, Macrocyclic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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