ArticleScience (New York, N.Y.)2017
Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474.
Article in Science (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 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.
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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.
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Who cites it
139 citing papers in PubMed, 323 citations in OpenAlex.
- Safety, Tolerability, and Pharmacokinetics of FAAH Inhibitor BIA 10-2474: A Double-Blind, Randomized, Placebo-Controlled Study in Healthy Volunteers.Clinical pharmacology and therapeutics · 2022Trial
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- 4-Oxo-2-Nonenal Crosslinks Vicinal Cysteine-Lysine Pairs in Cellular Proteins.Molecular & cellular proteomics : MCP · 2026Article
- Enhancing anandamide signalling through fatty acid amide hydrolase inhibition: An update on the pharmacological strategy for treating psychiatric disorders.Translational psychiatry · 2026Review
- α-Halothioamide warheads with enhanced cysteine reactivity and specificity for covalent protein labelling.Nature communications · 2026Article
- Unlocking the potential of computational phenotypic drug discovery: methods, challenges, and future directions.NPJ systems biology and applications · 2026Review
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- The Role of Cannabinoids and the Endocannabinoid System in the Treatment and Regulation of Nausea and Vomiting.Current topics in behavioral neurosciences · 2026Review
- Spatially Resolved Mapping of Monoacylglycerol Lipase Activity in the Brain.ACS chemical neuroscience · 2025Article
- Research Review: What we have learned about the endocannabinoid system in developmental psychopathology.Journal of child psychology and psychiatry, and allied disciplines · 2025Review
- Biocompatible Chemistry: A Plug-and-Play Toolbox for Chemical Biology Research.Chembiochem : a European journal of chemical biology · 2025Review
- Sulfoxide-diazirine (SODA) as a Cleavable Photoaffinity Group To Enable the Identification of Photolabeled Modification Sites via LC-MSAnalytical chemistry · 2025Article
- Probing the proteome.Nature biotechnology · 2025Article
- Advancing Covalent Ligand and Drug Discovery beyond Cysteine.Chemical reviews · 2025Review
- Review
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- Docking-Informed Machine Learning for Kinome-wide Affinity Prediction.Journal of chemical information and modeling · 2024Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 10 institutions in 4 countries.
Funding
Abstract
A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety profile of other tested FAAH inhibitors, that off-target activities of BIA 10-2474 may have played a role. Here we use activity-based proteomic methods to determine the protein interaction landscape of BIA 10-2474 in human cells and tissues. This analysis revealed that the drug inhibits several lipases that are not targeted by PF04457845, a highly selective and clinically tested FAAH inhibitor. BIA 10-2474, but not PF04457845, produced substantial alterations in lipid networks in human cortical neurons, suggesting that promiscuous lipase inhibitors have the potential to cause metabolic dysregulation in the nervous system.
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What OpenQuestion holds
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.