ArticleACS chemical biology2019
Global Portrait of Protein Targets of Metabolites of the Neurotoxic Compound BIA 10-2474.
Article in ACS chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
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- Imidazoles are Tunable Nucleofuges for Developing Tyrosine-Reactive Electrophiles.Chembiochem : a European journal of chemical biology · 2024Article
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- Comparative Analysis of Two NNMT Bisubstrate Inhibitors through Chemoproteomic Studies: Uncovering the Role of Unconventional SAM Analogue Moiety for Improved Selectivity.ACS chemical biology · 2024Article
- Thinking outside the CaaX-box: an unusual reversible prenylation on ALDH9A1.RSC chemical biology · 2023Article
- A protocol to visualize on-target specific drug binding in mammalian tissue with cellular resolution using tissue clearing and click chemistry.STAR protocols · 2022Article
- Phenotypic drug discovery: recent successes, lessons learned and new directions.Nature reviews. Drug discovery · 2022Review
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- Activity-Based Hydrazine Probes for Protein Profiling of Electrophilic Functionality in Therapeutic Targets.ACS central science · 2021Article
- Chemoproteomic methods for covalent drug discovery.Chemical Society reviews · 2021Review
- The endocannabinoid system - current implications for drug development.Journal of internal medicine · 2021Review
- Recent advances in activity-based probes (ABPs) and affinity-based probes (AChemical science · 2021Review
- Dipyridamole Inhibits Lipogenic Gene Expression by Retaining SCAP-SREBP in the Endoplasmic Reticulum.Cell chemical biology · 2021Article
- Positron Emission Tomography Imaging of the Endocannabinoid System: Opportunities and Challenges in Radiotracer Development.Journal of medicinal chemistry · 2021Review
- Bioorthogonal chemistry.Nature reviews. Methods primers · 2021Article
- A quantitative thiol reactivity profiling platform to analyze redox and electrophile reactive cysteine proteomes.Nature protocols · 2020Article
- Preclinical pharmacological evaluation of the fatty acid amide hydrolase inhibitor BIA 10-2474.British journal of pharmacology · 2020Article
- Click Chemistry in Proteomic Investigations.Cell · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Clinical investigation of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 resulted in serious adverse neurological events. Structurally unrelated FAAH inhibitors tested in humans have not presented safety concerns, suggesting that BIA 10-2474 has off-target activities. A recent activity-based protein profiling (ABPP) study revealed that BIA 10-2474 and one of its major metabolites inhibit multiple members of the serine hydrolase class to which FAAH belongs. Here, we extend these studies by performing a proteome-wide analysis of covalent targets of BIA 10-2474 metabolites. Using alkynylated probes for click chemistry-ABPP in human cells, we show that des-methylated metabolites of BIA 10-2474 covalently modify the conserved catalytic cysteine in aldehyde dehydrogenases, including ALDH2, which has been implicated in protecting the brain from oxidative stress-related damage. These findings indicate that BIA 10-2474 and its metabolites have the potential to inhibit multiple mechanistically distinct enzyme classes involved in nervous system function.
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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.