ArticleACS chemical biology2014
Exploring a 2-naphthoic acid template for the structure-based design of P2Y14 receptor antagonist molecular probes.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Computational discovery and repurposing of chloramphenicol succinate as a potent P2YJournal of advanced research · 2026Article
- P2YACS pharmacology & translational science · 2025Article
- Drug-like Antagonists of P2Y Receptor Subtypes: An Update.Journal of medicinal chemistry · 2025Review
- Chimeras Derived from a P2YACS pharmacology & translational science · 2024Article
- Stereocontrolled access to thioisosteres of nucleoside di- and triphosphates.Nature chemistry · 2024Article
- Alicyclic Ring Size Variation of 4-Phenyl-2-naphthoic Acid Derivatives as P2YJournal of medicinal chemistry · 2023Article
- Bridged Piperidine Analogues of a High Affinity Naphthalene-Based P2YJournal of medicinal chemistry · 2022Article
- Structure-Activity Relationship of Heterocyclic P2YJournal of medicinal chemistry · 2021Article
- Purinergic Signaling: Impact of GPCR Structures on Rational Drug Design.ChemMedChem · 2020Review
- Exploration of Alternative Scaffolds for P2YJournal of medicinal chemistry · 2020Article
- P2YACS medicinal chemistry letters · 2020Article
- Discovery of novel and potent P2YJournal of advanced research · 2020Article
- Molecular Modeling Applied to the Discovery of New Lead Compounds for P2 Receptors Based on Natural Sources.Frontiers in pharmacology · 2020Review
- Structure-Guided Modification of Heterocyclic Antagonists of the P2YJournal of medicinal chemistry · 2018Article
- Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug Design.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Nucleoside 5'-O-monophosphorothioates as modulators of the P2Y14 receptor and mast cell degranulation.Oncotarget · 2016Article
- Structure-Based Design of 3-(4-Aryl-1H-1,2,3-triazol-1-yl)-Biphenyl Derivatives as P2Y14 Receptor Antagonists.Journal of medicinal chemistry · 2016Article
- Medicinal chemistry of adenosine, P2Y and P2X receptors.Neuropharmacology · 2016Review
- New paradigms in GPCR drug discovery.Biochemical pharmacology · 2015Review
- Lighting up G protein-coupled purinergic receptors with engineered fluorescent ligands.Neuropharmacology · 2015Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The P2Y14 receptor (P2Y14R), one of eight P2Y G protein-coupled receptors (GPCR), is involved in inflammatory, endocrine, and hypoxic processes and is an attractive pharmaceutical target. The goal of this research is to develop high-affinity P2Y14R fluorescent probes based on the potent and highly selective antagonist 4-(4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl)-2-naphthoic acid (6, PPTN). A model of hP2Y14R based on recent hP2Y12R X-ray structures together with simulated antagonist docking suggested that the piperidine ring is suitable for fluorophore conjugation while preserving affinity. Chain-elongated alkynyl or amino derivatives of 6 for click or amide coupling were synthesized, and their antagonist activities were measured in hP2Y14R-expressing CHO cells. Moreover, a new Alexa Fluor 488 (AF488) containing derivative 30 (MRS4174, Ki = 80 pM) exhibited exceptionally high affinity, as compared to 13 nM for the alkyne precursor 22. A flow cytometry assay employing 30 as a fluorescent probe was used to quantify specific binding to P2Y14R. Known P2Y receptor ligands inhibited binding of 30 with properties consistent with their previously established receptor selectivities and affinities. These results illustrate that potency in this series of 2-naphthoic acid derivatives can be preserved by chain functionalization, leading to highly potent fluorescent molecular probes for P2Y14R. Such conjugates will be useful tools in expanding the SAR of this receptor, which still lacks chemical diversity in its collective ligands. This approach demonstrates the predictive power of GPCR homology modeling and the relevance of newly determined X-ray structures to GPCR medicinal chemistry.
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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.