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P2Y receptor antagonists and agonists act on purinergic G protein-coupled receptors for extracellular nucleotides. The eight human P2Y receptors respond to adenosine diphosphate (ADP), adenosine triphosphate (ATP), uridine triphosphate (UTP) or related nucleotides. The first member, now called P2Y1, was cloned from chick brain in 1993 as a G protein-coupled ATP receptor. In 2001 the platelet ADP receptor P2Y12 was identified as the target of thienopyridine antithrombotic compounds. Clopidogrel hydrogen sulfate and prasugrel are thienopyridine prodrugs, whereas ticagrelor, cangrelor and AZD1283 block P2Y12 without metabolic activation. BPTU is an allosteric P2Y1 antagonist, and MRS 2578 blocks P2Y6, a receptor activated by uridine diphosphate. Ligand-gated nucleotide channels are listed separately under the sibling category P2X Receptor.
Synonyms: INS365
Diquafosol tetrasodium is a potent P2Y2 receptor agonist. It enhances fluid and mucin secretion on the ocular surface, making it an effective topical therapeutic option for the management of dry eye disease. This compound is valuable for research applications focused on ocular health and pharmacological interventions for dry eye conditions.
PSB 0474 (3-phenacyl-UDP) is a selective and potent agonist of the P2Y6 receptor, exhibiting an EC50 of 70 nM. This compound modulates key biological activities, including the inhibition of cell proliferation and the enhancement of nitric oxide release in astrocytes and microglia. Additionally, PSB 0474 promotes apoptosis in astrocytes, making it a valuable tool for research in neurobiology and cell signaling pathways.
MRS2693 ammonium is a selective agonist targeting the P2Y6 receptor, exhibiting an EC50 of 0.015 μM. This compound demonstrates significant biological activity by protecting C2C12 skeletal muscle cells from TNFα-induced apoptosis and reducing NF-kB activation. Additionally, MRS2693 ammonium activates the ERK1/2 signaling pathway and has shown cytoprotective effects in a mouse model of ischemia-reperfusion injury, making it a valuable tool for research in cellular protection and signaling pathways.
Synonyms: INS365 free base
Diquafosol is a potent P2Y2 receptor agonist that plays a significant role in modulating cellular responses associated with inflammation and apoptosis. It exhibits the ability to inhibit apoptotic pathways and reduce reactive oxygen species (ROS) generation, thereby promoting cell survival. Diquafosol is primarily used in research related to dry eye therapies, providing valuable insights into potential treatment strategies for this condition.
MRS2693 trisodium is a selective agonist of the P2Y6 receptor, exhibiting an EC50 value of 0.015 μM. It significantly reduces NF-kappaB activation while activating the ERK1/2 signaling pathway. MRS2693 trisodium demonstrates cytoprotective effects in models of ischemia-reperfusion injury in mouse hindlimb skeletal muscle, making it a valuable tool for research in cellular signaling and tissue injury responses.
Uridine-5'-diphosphate disodium salt functions as an agonist for the P2Y6 receptor, exhibiting high specificity with an EC50 of 300 nM (pEC50=6.52 for the human P2Y6 receptor). This endogenous metabolite plays a crucial role in catalyzing the glucuronidation of various substrates and is also instrumental in RNA biosynthesis. Its modulation of P2Y receptors has significant implications for research in cellular signaling and metabolic processes.
MRS2690 is a selective agonist of the P2Y14 receptor, primarily known for its role in the inhibition of adenylyl cyclase activity, which leads to a reduction in intracellular cAMP levels. This compound mediates concentration-dependent vasoconstriction in porcine coronary arteries and induces intracellular calcium mobilization. Additionally, MRS2690 activates p38 MAPK and stimulates [35S]GTPγS binding in RBL-2H3 cell membranes. It also enhances β-hexosaminidase release in response to antigen and complement activation, making it a valuable tool for research in ischemic heart disease.
Synonyms: Adenosine-5'-O-(3-thiotriphosphate) tetralithium salt; Adenosine 5'-[γ-thio]triphosphate tetralithium salt
ATPγS tetralithium salt is a highly effective agonist of the P2Y11 receptor, playing a pivotal role in various cellular signaling pathways. This compound exhibits notable antioxidant properties and provides neuroprotection, enhancing its utility in neuroscience research. Additionally, ATPγS serves as a substrate for nucleotide hydrolysis and RNA unwinding activities mediated by the eukaryotic translation initiation factor eIF4A, making it valuable for studies related to translation and RNA biology. Its activity in ATP hydrolysis further supports its application in metabolic research.
ATP-γ-S tetrasodium is a potent agonist of the P2Y11 receptor, known for its antioxidant and neuroprotective properties. This compound serves as a substrate for nucleotide hydrolysis and facilitates RNA unwinding activities of the eukaryotic translation initiation factor eIF4A. Additionally, ATP-γ-S tetrasodium demonstrates significant activity in ATP hydrolysis, making it valuable for studies in cellular signaling and translational control.
MRS2365 is a highly potent and selective agonist of the P2Y1 receptor, exhibiting an EC50 of 0.4 nM for [35S]GTPγS binding and β-arrestin 2 recruitment. This compound effectively alleviates mechanical allodynia and enhances mechanical sensitivity, making it valuable for pain research. Notably, MRS2365 demonstrates minimal activity at P2Y12 and P2Y13 receptors, highlighting its specificity for P2Y1.
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Synonyms: UDP-D-Glucose disodium
Uridine 5'-diphosphoglucose disodium is a potent agonist of the P2Y14 receptor, which plays a critical role in the regulation of inflammation and neutrophil polarization in response to ischemic conditions. Secreted by cardiomyocytes, this compound is involved in the synthesis of glucose-containing oligosaccharides, polysaccharides, glycoproteins, and glycolipids in various biological systems. Its ability to modulate inflammatory responses makes Uridine 5'-diphosphoglucose disodium a valuable reagent for studies focused on myocardial infarction and reperfusion-induced inflammation.
UDP-Galactose disodium is a potent agonist of the P2Y14 receptor, demonstrating an EC50 of 0.67 μM for the human variant. This compound serves as a substrate for the enzyme beta-1,4 galactosyltransferase V (B4GALT5), playing a critical role in glycosylation processes. Additionally, UDP-Galactose disodium is essential for the biosynthesis of various glycoconjugates that contribute to the surface glycocalyx of Leishmania major, making it valuable for research in cell signaling and pathogen biology.
Synonyms: 2-Methylthioadenosine diphosphate trisodium; 2-Methylthio-ADP trisodium
2-Methylthioadenosine diphosphate trisodium is a potent agonist of purinergic P2Y receptors, specifically exhibiting EC50 values of 19 nM, 6.2 nM, and 5 nM for human P2Y13, mouse P2Y13, and human P2Y12, respectively. Additionally, it demonstrates pEC50 values of 8.29 and 5.75 for human P2Y1 and rat P2Y6, respectively. This compound is known to induce platelet aggregation and morphological changes while inhibiting cyclic AMP accumulation in platelets in the presence of prostaglandin E1, making it a valuable tool for research in platelet function and signaling pathways.
Synonyms: 4-Thio-UTP tetralithium
4-Thiouridine 5′-triphosphate tetralithium is a potent agonist for the P2Y2 and P2Y4 receptors, demonstrating EC50 values of 35 nM and 350 nM, respectively. This UTP analog is utilized in various research applications, including cross-linking experiments and transcriptional complex labeling studies, making it an essential tool for investigating nucleic acid interactions and cell signaling pathways.
MRS2768 tetrasodium salt is a selective agonist for the P2Y2 receptor. This compound demonstrates protective effects on cardiomyocytes against ischemic damage both in vivo and in vitro, making it a valuable tool for research into cardiovascular diseases. Its ability to activate P2Y2 receptors can aid in studying various biological processes related to cell survival and tissue protection.
NF546 is a selective non-nucleotide agonist of the P2Y11 receptor, exhibiting a pEC50 of 6.27. This compound effectively stimulates the release of interleukin-8 from human monocyte-derived dendritic cells, making it valuable for research focused on immune response modulation and inflammation pathways. Its targeted action on P2Y11 highlights its potential in studying purinergic signaling and associated biological functions.
Synonyms: UTPγS trisodium
Uridine-5'-O-(3-thiotriphosphate) trisodium is a stable analogue of UTP that acts as a potent agonist of the P2Y2 and P2Y4 receptors. Its increased metabolic stability enhances its effectiveness in various biological studies. This compound is valuable for research applications involving purinergic signaling and receptor physiology.
UTPU trisodium is a selective agonist of the P2Y6 receptor, exhibiting an EC50 of 0.4 μM. This compound effectively activates intracellular calcium signaling pathways mediated by P2Y6, making it a valuable tool for studying inflammatory processes. UTPU trisodium is suitable for research applications focused on inflammation and related signaling mechanisms.
MRS2957 is a selective agonist of the P2Y6 receptor, which plays a crucial role in activating AMP-activated protein kinase (AMPK) in pancreatic β-cells. This activation promotes insulin secretion while reducing apoptosis, highlighting its potential as a therapeutic target for type 2 diabetes. MRS2957 may provide valuable insights in research focused on diabetes treatment and pancreatic function.
UDP-Galactose is a glycosyl donor molecule and a natural agonist of the P2Y14 receptor, which is coupled to Gi proteins in immune responses. It exhibits significant biological activity with an IC50 value of 0.67 μM for human P2Y14 receptor activation. This reagent is valuable for research applications investigating cell signaling pathways and nucleotide sugar metabolism.
mrs 4062 TEA is a selective agonist of the P2Y4 receptor, exhibiting a potent EC50 of 23 nM. This compound also demonstrates moderate activity against the P2Y2 and P2Y6 receptors, with EC50 values of 640 nM and 740 nM, respectively. mrs 4062 TEA is valuable in research focused on purinergic signaling and its implications in various physiological processes and disease states.
Synonyms: 2-Methylthioadenosine diphosphate; 2-Methylthio-ADP
2-MeSADP is a potent agonist for P2Y receptors, exhibiting an EC50 of 5 nM for human P2Y12 and EC50 values of 19 nM and 13 nM for human P2Y13, with an EC50 of 6.2 nM for mouse P2Y13. This compound preferentially activates P2Y12 over P2Y13 and induces increases in intracellular calcium levels, Gi-mediated cAMP inhibition, and adenylate cyclase inhibition, facilitating downstream signaling pathways. 2-MeSADP is suitable for investigations into various biological processes, including research related to glaucoma.
Synonyms: 2-Thiouridine 5′-triphosphate tetrasodium
2-Thio-UTP tetrasodium is a potent agonist of the P2Y2, P2Y4, and P2Y6 receptors. It plays a crucial role in cell signaling pathways involved in cancer research, facilitating the study of tumor microenvironments and cellular responses. This compound is valuable for investigating therapeutic targets related to purinergic signaling in various cancers.
PSB-1114 tetrasodium is a potent agonist of the P2Y2 receptor, exhibiting an EC50 of 134 nM and demonstrating significant enzymatic stability. This compound is highly selective, showing over 50-fold selectivity against the P2Y4 and P2Y6 receptors, with EC50 values of 9.3 μM and 7.0 μM, respectively. PSB-1114 tetrasodium is valuable for research applications focusing on P2Y2 receptor-mediated signaling pathways and related physiological processes.
Synonyms: 5-Methoxyuridine 5'-trihydrogen diphosphate
5-OMe-UDP, a potent P2Y6 receptor agonist with an EC50 of 0.08 μM, activates the P2Y6 receptor by binding and initiating intracellular signaling cascades. This activation results in increased intracellular calcium ion concentration, influencing various cellular functions. The presence of methoxy groups in 5-OMe-UDP enhances its selectivity and activity, making it a valuable tool for investigating pathologies associated with P2Y6 receptor function, including diabetes, inflammatory bowel disease, and Alzheimer's disease.
