ArticleCellular and molecular life sciences : CMLS2023
Inhibiting a promiscuous GPCR: iterative discovery of bitter taste receptor ligands.
Article in Cellular and molecular life sciences : CMLS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 33 citations in OpenAlex.
- Taste Modulation by Umami Compounds: Mechanisms, Sensor-Based Evaluation, and Pharmaceutical Applications in Bitterness Suppression.Sensors (Basel, Switzerland) · 2026Review
- Bitter taste TAS2R14 and TAS2R46 receptors bound to G proteins: comparison of cryo-EM, AlphaFold, and molecular dynamics structures.European biophysics journal : EBJ · 2026Article
- Intracellular and dual-site inhibition of a bitter taste GPCR.Cellular and molecular life sciences : CMLS · 2026Article
- T2R5 Agonist Phendione Decreases Cell Viability and Induces Apoptosis in Head and Neck Squamous Cell Carcinoma.Molecular cancer therapeutics · 2026Article
- Quercetin as a Bitter Taste Receptor Agonist with Anticancer Effects in Head and Neck Cancer Cells.Nutrients · 2025Article
- The appearance of bitter taste receptors - inspiration from structure, expression, function, and mechanism.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Article
- Chemosensory role of intracellular TAS2Rs, the activation of which triggers drug excretion by ABCB1 in cancer cells.Scientific reports · 2025Article
- A deadly taste: linking bitter taste receptors and apoptosis.Apoptosis : an international journal on programmed cell death · 2025Review
- Hops bitter β-acids have antibacterial effects against sinonasal Staphylococcus aureus but also induce sinonasal cilia and mitochondrial dysfunction.International forum of allergy & rhinology · 2025Article
- Bitter taste receptors.Chemical senses · 2025Review
- Bitter taste receptors in the gut-vascular axis: a novel target for immune and metabolic regulation of hypertension.Frontiers in immunology · 2025Review
- Neuropeptidergic systems in psychiatric disorders.Frontiers in endocrinology · 2025Review
- A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR.Nature communications · 2024Article
- Identification of 4'-Demethyl-3,9-dihydroeucomin as a Bitter-Masking Compound from the Resin ofJournal of agricultural and food chemistry · 2024Article
- The Art and Science of Molecular Docking.Annual review of biochemistry · 2024Review
- The Growing Complexity of Human Bitter Taste Perception.Journal of agricultural and food chemistry · 2024Review
- Article
- Intestinal Taste Receptor Expression and Its Implications for Health: An Integrative Analysis in Female Rats after Chronic Insect Supplementation.Journal of agricultural and food chemistry · 2024Article
- Membrane-bound chemoreception of bitter bile acids and peptides is mediated by the same subset of bitter taste receptors.Cellular and molecular life sciences : CMLS · 2024Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The human GPCR family comprises circa 800 members, activated by hundreds of thousands of compounds. Bitter taste receptors, TAS2Rs, constitute a large and distinct subfamily, expressed orally and extra-orally and involved in physiological and pathological conditions. TAS2R14 is the most promiscuous member, with over 150 agonists and 3 antagonists known prior to this study. Due to the scarcity of inhibitors and to the importance of chemical probes for exploring TAS2R14 functions, we aimed to discover new ligands for this receptor, with emphasis on antagonists. To cope with the lack of experimental structure of the receptor, we used a mixed experimental/computational methodology which iteratively improved the performance of the predicted structure. The increasing number of active compounds, obtained here through experimental screening of FDA-approved drug library, and through chemically synthesized flufenamic acid derivatives, enabled the refinement of the binding pocket, which in turn improved the structure-based virtual screening reliability. This mixed approach led to the identification of 10 new antagonists and 200 new agonists of TAS2R14, illustrating the untapped potential of rigorous medicinal chemistry for TAS2Rs. 9% of the ~ 1800 pharmaceutical drugs here tested activate TAS2R14, nine of them at sub-micromolar concentrations. The iterative framework suggested residues involved in the activation process, is suitable for expanding bitter and bitter-masking chemical space, and is applicable to other promiscuous GPCRs lacking experimental structures.
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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.