ArticleNature chemical biology2016
Discovery of allosteric modulators for GABAA receptors by ligand-directed chemistry.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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Who cites it
18 citing papers in PubMed.
- Chemical reactions for the ligand-directed modification of native proteins.Chemical Society reviews · 2026Review
- Redox-Activated Probes Enable High-Contrast Live Imaging of Native Postsynaptic Scaffolds.Angewandte Chemie (International ed. in English) · 2026Article
- Biocompatible sulfonium-based covalent probes for endogenous tubulin fluorescence nanoscopy in live and fixed cells.Nature communications · 2025Article
- Target Bioconjugation of Protein Through Chemical, Molecular Dynamics, and Artificial Intelligence Approaches.Metabolites · 2024Review
- Imidazoles are Tunable Nucleofuges for Developing Tyrosine-Reactive Electrophiles.Chembiochem : a European journal of chemical biology · 2024Article
- Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Phenols and GABAFrontiers in pharmacology · 2024Review
- Protein-protein interactions: developing small-molecule inhibitors/stabilizers through covalent strategies.Trends in pharmacological sciences · 2023Review
- Chemically programmable bacterial probes for the recognition of cell surface proteins.Materials today. Bio · 2023Article
- Small molecule photocatalysis enables drug target identification via energy transfer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Ultrafast and selective labeling of endogenous proteins using affinity-based benzotriazole chemistry.Chemical science · 2022Article
- Recent advances in construction of small molecule-based fluorophore-drug conjugates.Journal of pharmaceutical analysis · 2020Review
- Fluorescence imaging of drug target proteins using chemical probes.Journal of pharmaceutical analysis · 2020Review
- Looking for Novelty in an "Old" Receptor: Recent Advances Toward Our Understanding of GABAFrontiers in neuroscience · 2020Review
- Visualizing endogenous opioid receptors in living neurons using ligand-directed chemistry.eLife · 2019Article
- Construction of a Fluorescent Screening System of Allosteric Modulators for the GABAACS central science · 2019Article
- Rapid labelling and covalent inhibition of intracellular native proteins using ligand-directed N-acyl-N-alkyl sulfonamide.Nature communications · 2018Article
- Analytical Techniques in Neuroscience: Recent Advances in Imaging, Separation, and Electrochemical Methods.Analytical chemistry · 2017Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The fast inhibitory actions of γ-aminobutyric acid (GABA) are mainly mediated by GABAA receptors (GABAARs) in the brain. The existence of multiple ligand-binding sites and a lack of structural information have hampered the efficient screening of drugs capable of acting on GABAARs. We have developed semisynthetic fluorescent biosensors for orthosteric and allosteric GABAAR ligands on live cells via coupling of affinity-based chemical labeling reagents to a bimolecular fluorescence quenching and recovery system. These biosensors were amenable to the high-throughput screening of a chemical library, leading to the discovery of new small molecules capable of interacting with GABAARs. Electrophysiological measurements revealed that one hit, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), was a novel negative allosteric modulator capable of strongly suppressing GABA-induced chloride currents. Thus, these semisynthetic biosensors represent versatile platforms for screening drugs to treat GABAAR-related neurological disorders, and this strategy can be extended to structurally complicated membrane proteins.
Indexed as
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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.