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Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor.
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Exploring the Mode-of-Action of Bioactive Compounds by Chemical-Genetic Profiling in Yeast
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Effects of nutrient limitation on toxin production and composition in the marine dinoflagellate Protogonyaulax tamarensis
TLDR
Eventhough dramatic effects on the total toxin concentration were observed in response to nutrient limitation (N or P), the toxin composition (on a percent basis) remained constant, suggesting that the individual toxin composition of a given isolate is a fixed genetic trait and not a transient response to changing environmental factors.
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Bioaccumulation and clearance of microcystins from salt water mussels, Mytilus edulis, and in vivo evidence for covalently bound microcystins in mussel tissues.
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Evidence for a covalently bound form of microcystin-LR in salmon liver and Dungeness crab larvae.
TLDR
The Lemieux oxidation-GC/MS method detected 10,000-fold greater microcystin concentrations in Cypress Island Dungeness crab larvae than did the MeOH extraction-PPase method, and is taken as direct evidence for the existence of covalently boundmicrocystins in vivo.
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An androgen receptor N-terminal domain antagonist for treating prostate cancer.
TLDR
Investigation of EPI-001 finds that EPI analogs covalently bound the NTD to block transcriptional activity of AR and its splice variants and reduced the growth of CRPC xenografts, suggesting that the development of small-molecule inhibitors that bind covalent to intrinsically disordered proteins is a promising strategy for development of specific and effective anticancer agents.
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Chemical and biological evidence links microcystins to salmon 'netpen liver disease'.
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A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds
TLDR
A yeast chemical-genomics approach designed to identify genes that when mutated confer drug resistance, thereby providing insight about the modes of action of compounds is presented, and a new class of sterol-binding compounds is discovered.
View on Nature
Novel natural products from soil DNA libraries in a streptomycete host.
As a route to accessing the potential chemical diversity of uncultivable microbes from the soil, combinatorial biosynthetic libraries were constructed by cloning large fragments of DNA isolated from…
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The Search for Novel Human Pancreatic α‐Amylase Inhibitors: High‐Throughput Screening of Terrestrial and Marine Natural Product Extracts
TLDR
A family of three glycosylated acyl flavonols, montbretins A–C, was thereby identified and characterized as competitive amylase inhibitors, with Ki values ranging from 8.1–6100 nM, which suggest a binding mode for these inhibitors.
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