ArticleBioorganic & medicinal chemistry2008
Novel inhibitors of anthrax edema factor.
Article in Bioorganic & medicinal chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Fused Tetrahydroquinolines Are Interfering with Your Assay.Journal of medicinal chemistry · 2023Review
- Novel eIF4A1 inhibitors with anti-tumor activity in lymphoma.Molecular medicine (Cambridge, Mass.) · 2022Article
- Repurposing approved drugs on the pathway to novel therapies.Medicinal research reviews · 2020Review
- Allosteric inhibitors of Coxsackie virus A24 RNA polymerase.Bioorganic & medicinal chemistry · 2016Article
- In Silico Genomic Fingerprints of the Bacillus anthracis Group Obtained by Virtual Hybridization.Microarrays (Basel, Switzerland) · 2015Article
- An overview of investigational toxin-directed therapies for the adjunctive management of Bacillus anthracis infection and sepsis.Expert opinion on investigational drugs · 2015Review
- Designing inhibitors of anthrax toxin.Expert opinion on drug discovery · 2014Review
- Computational methods in drug discovery.Pharmacological reviews · 2014Review
- Pharmacophore selection and redesign of non-nucleotide inhibitors of anthrax edema factor.Toxins · 2012Review
- Review
- Structural basis of anthrax edema factor neutralization by a neutralizing antibody.Biochemical and biophysical research communications · 2012Article
- Structure-based redesign of an edema toxin inhibitor.Bioorganic & medicinal chemistry · 2012Article
- Use of allostery to identify inhibitors of calmodulin-induced activation of Bacillus anthracis edema factor.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Testing the efficacy and toxicity of adenylyl cyclase inhibitors against enteric pathogens using in vitro and in vivo models of infection.Infection and immunity · 2010Article
- Effects of introducing a single charged residue into the phenylalanine clamp of multimeric anthrax protective antigen.The Journal of biological chemistry · 2010Article
- Docking and chemoinformatic screens for new ligands and targets.Current opinion in biotechnology · 2009Review
- Computational selection of inhibitors of Abeta aggregation and neuronal toxicity.Bioorganic & medicinal chemistry · 2009Article
- A library of novel allosteric inhibitors against fructose 1,6-bisphosphatase.Bioorganic & medicinal chemistry · 2009Article
- Docking screens: right for the right reasons?Current topics in medicinal chemistry · 2009Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Several pathogenic bacteria produce adenylyl cyclase toxins, such as the edema factor (EF) of Bacillus anthracis. These disturb cellular metabolism by catalyzing production of excessive amounts of the regulatory molecule cAMP. Here, a structure-based method, where a 3D-pharmacophore that fit the active site of EF was constructed from fragments, was used to identify non-nucleotide inhibitors of EF. A library of small molecule fragments was docked to the EF-active site in existing crystal structures, and those with the highest HINT scores were assembled into a 3D-pharmacophore. About 10,000 compounds, from over 2.7 million compounds in the ZINC database, had a similar molecular framework. These were ranked according to their docking scores, using methodology that was shown to achieve maximum accuracy (i.e., how well the docked position matched the experimentally determined site for ATP analogues in crystal structures of the complex). Finally, 19 diverse compounds with the best AutoDock binding/docking scores were assayed in a cell-based assay for their ability to reduce cAMP secretion induced by EF. Four of the test compounds, from different structural groups, inhibited in the low micromolar range. One of these has a core structure common to phosphatase inhibitors previously identified by high-throughput assays of a diversity library. Thus, the fragment-based pharmacophore identified a small number of diverse compounds for assay, and greatly enhanced the selection process of advanced lead compounds for combinatorial design.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.