ArticleBiochemical pharmacology2004
Diisothiocyanate derivatives as potent, insurmountable antagonists of P2Y6 nucleotide receptors.
Article in Biochemical pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 165 citations in OpenAlex.
- Investigation of reported small molecule P2Y6 receptor antagonists.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
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- Nitric oxide modulates UDP-evoked cytosolic transients via P2YScientific reports · 2025Article
- Pericyte pannexin1 controls cerebral capillary diameter and supports memory function.Nature communications · 2025Article
- Applications of artificial intelligence in drug discovery for neurological diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics.Journal of advanced research · 2025Review
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- The microglial P2YTranslational neurodegeneration · 2024Review
- Functionalized Congeners of 2Cells · 2024Article
- Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.Purinergic signalling · 2024Review
- Pharmacological characterization of P2Y receptor subtypes - an update.Purinergic signalling · 2024Review
- ATP purinergic receptor signalling promotes Sca-1Cell communication and signaling : CCS · 2023Article
- Involvement of P2YCells · 2023Article
- P2YAging cell · 2023Article
- Characterisation of P2Y receptor subtypes mediating vasodilation and vasoconstriction of rat pulmonary artery using selective antagonists.Purinergic signalling · 2022Article
- Synthesis and pharmacological characterization of multiply substituted 2H-chromene derivatives as P2YBioorganic & medicinal chemistry letters · 2022Article
- Mechanisms of sympathoexcitationFrontiers in pharmacology · 2022Article
- Recommended tool compounds and drugs for blocking P2X and P2Y receptors.Purinergic signalling · 2021Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The physiological role of the P2Y(6) nucleotide receptor may involve cardiovascular, immune and digestive functions based on the receptor tissue distribution, and selective antagonists for this receptor are lacking. We have synthesized a series of symmetric aryl diisothiocyanate derivatives and examined their ability to inhibit phospholipase C (PLC) activity induced by activation of five subtypes of recombinant P2Y receptors. Several derivatives were more potent at inhibiting action of UDP at both human and rat P2Y(6) receptors expressed in 1321N1 human astrocytes than activation of human P2Y(1), P2Y(2), P2Y(4) and P2Y(11) receptors. The inhibition by diisothiocyanate derivatives of 1,2-diphenylethane (MRS2567) and 1,4-di-(phenylthioureido) butane (MRS2578) was concentration-dependent and insurmountable, with IC(50) values of 126+/-15 nM and 37+/-16 nM (human) and 101+/-27 nM and 98+/-11 nM (rat), respectively. A derivative of 1,4-phenylendiisothiocyanate (MRS2575) inhibited only human but not rat P2Y(6) receptor activity. MRS2567 and MRS2578 at 10microM did not affect the UTP (100nM)-induced responses of cells expressing P2Y(2) and P2Y(4) receptors, nor did they affect the 2-methylthio-ADP (30nM)-induced responses at the P2Y(1) receptor or the ATP (10microM)-induced responses at the P2Y(11) receptor. Other antagonists displayed mixed selectivities. The selective antagonists MRS2567, MRS2575 and MRS2578 (1microM) completely blocked the protection by UDP of cells undergoing TNFalpha-induced apoptosis. Thus, we have identified potent, insurmountable antagonists of P2Y(6) receptors that are selective within the family of PLC-coupled P2Y receptors.
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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.