purinergic

Clodronate disodium tetrahydrate (Clastoban) inhibits bone resorption and soft tissue calcification.

This novel compound is an orally bioavailable antagonist of P2X3/P2X2/3 receptors, exhibiting potent activity with a pIC50 of 8 in both human and rat, and a pIC50 of 7.3 specifically for the human P2X2/3 receptor. It demonstrates high brain penetration, evidenced by a brain to plasma ratio of 6, and effectively blocks agonist-evoked intracellular Ca2+ flux and inward currents within the nanomolar range (10 nM to 1 µM) in cell lines that express human P2X3 and P2X2/3 receptors recombinantly. The compound also shows favorable pharmacokinetic properties, with a half-life (t1/2) of 1.63 hours and a time to reach maximum concentration (Tmax) of 30 minutes.

ATP (Adenosine triphosphate) provides cellular energy, participates in overall energy balance, and maintains intracellular homeostasis. ATP can act as an extracellular signaling molecule through interactions with specific purinergic receptors to mediate a variety of processes including neurotransmission, inflammation, apoptosis, and bone remodeling.

L-Methionine sulfoxide (H-Met(O)-OH) is a metabolite of Methionine that modulates oxidative stress and purinergic signaling parameters, while inducing M1/classical macrophage polarization.

Tanshinone IIA sulfonate sodium (Tanshinone IIA sodium sulfonate) is a water-soluble derivative of tanshinone IIA extracted from Savia miltiorrhiza; a potent negative allosteric modulator of the human purinergic receptor P2X7. Tanshinone IIA sulfonate sodium (12.5 μM) inhibits hypoxia-induced PKG and PPAR-γ downregulation in PASMCs and distal pulmonary arteries of rats.

Neocuproine is a copper(I) chelator that enhances the purinergic component of vasoconstriction induced by electric field stimulation, and is often used as a ligand reagent and copper ion detector.Neocuproine forms stable complexes with copper ions and can play a catalytic role in certain chemical reactions and analytical methods.Neocuproine acts as a redox-active on the iron and cobalt ligand platform for protection against oxidative damage in NSC34 cells.

CTP disodium dihydrate is an agonist of P2X4 purinergic receptor

Indophagolin is a potent, indoline-containing autophagy inhibitor with an IC50 of 140 nM, and it antagonizes the purinergic receptor P2X4 as well as P2X1 and P2X3 with IC50s of 2.71, 2.40, and 3.49 μM, respectively.

Uridine triphosphate (UTP) is a purine nucleotide P2U receptor agonist with potential use in lung cancer treatment. By activating P2Y2 receptors, it enhances the proliferation of human cancerous ductal epithelial cells. Additionally, UTP induces fibrotic responses in cardiac fibroblasts through P2Y2 receptor activation and prolongs the action potential duration of guinea pig papillary muscles via the P2Y2 purinergic receptor.

2-MeSADP (2-Methylthioadenosine diphosphate; 2-Methylthio-ADP) is a potent agonist of purinergic (P2Y) receptors, displaying EC50 values of 19 nM for human P2Y13, 6.2 nM for mouse P2Y13, and 5 nM for human P2Y12. It also has pEC50 values of 8.29 for human P2Y1 and 5.75 for rat P2Y6. 2-MeSADP induces platelet aggregation and morphological changes, while inhibiting the accumulation of cyclic adenosine monophosphate in platelets in the presence of prostaglandin E1.

TNP-ATP is an antagonist of purinergic P2Y1, P2X3, and P2X2/3 receptors, exhibiting IC50 values of 6, 0.9, and 7 nM, respectively, in HEK293 cells expressing human receptors. It reduces acetic acid-induced calcium flux in 1321N1 cells expressing P2X3 and P2X2/3 receptors with IC50 values of 100 and 62 nM, respectively. TNP-ATP also dose-dependently alleviates acetic acid-induced writhing responses in a visceral pain model in mice, with an ED50 of 6.35 µmol/kg.

Uridine 5'-O-thiodiphosphate (trisodium) (UDP-β-S (trisodium)) acts as an agonist for the purinergic P2Y6 receptor. This compound selectively induces the accumulation of inositol phosphate in 1321N1 cells expressing P2Y6 receptors, with an EC50 value of 28 nM. Additionally, it stimulates DNA synthesis in rat aortic smooth muscle cells.

Rp-dUTPαS (tetrasodium) is an isomer of the sulfur-containing nucleotide dUTP-α-S and acts as an agonist of the purinergic P2Y2 receptor. It selectively induces the accumulation of inositol phosphates in P2Y2-expressing 1321N1 cells with an EC50 of 12.5 μM.

Rp-UTP-α-S (tetrasodium) is a nucleotide agonist of the purinergic P2Y2 and P2Y4 receptors. It can induce the accumulation of inositol phosphate in 1321N1 cells expressing P2Y2 or P2Y4, with EC50 values of 5.4 and 27 μM, respectively.

HDB-1 is a selective inhibitor of the P2Y14 receptor (P2Y14R) with an IC50 of 26 pM. HDB-1 shows no significant inhibition on P2Y1R, P2Y2R, P2Y4R, P2Y6R, and P2Y12R. HDB-1 blocks the activation of hepatic stellate cells (HSC) by inhibiting the PKA/Raf1/MEK/ERK signaling pathway mediated by P2Y14R, thereby alleviating the core pathological process of liver fibrosis. HDB-1 is used in liver fibrosis research models to investigate purinergic receptor signaling specificity, hepatic stellate cell activation pathways, and downstream MAPK pathway modulation in fibrogenesis-related cellular systems.

Uridine-5'-O-(3-thiotriphosphate) tetrasodium (UTPγS) is a stable analog of Uridine triphosphate (UTP) and acts as a potent agonist for P2Y2 and P2Y4 receptors, offering enhanced metabolic stability. It can stimulate the generation of inositol phosphates in 1321N1 astrocytoma cells, which stably express phospholipase C-coupled human P2U purinergic receptors (EC50= 240 nM).

2-Thio-UTP is a selective P2Y2 receptor (purinergic receptor) agonist (EC50 = 50 nM) capable of inhibiting calcification potential, α-smooth muscle actin expression, and pro-fibrotic gene expression in valvular interstitial cells (VICs). It may be employed in studies of calcific aortic valve stenosis (CAVS).

PIT (2,2'-Pyridylisatogen tosylate) is a specific, non-competitive antagonist of the Purinergic receptor P2Y1, exhibiting an IC50 of 0.14 μM for human P2Y1. It does not affect nucleotide binding and is useful in studies related to chronic bronchitis and asthma.

P2X1 purinergic receptor antagonist

2-Methylthioadenosine diphosphate trisodium (2-MeS-ADP) is the salt form of 2-Methylthioadenosine diphosphate, a synthetic analog of adenosine diphosphate (ADP), a potent purinergic P2Y receptor agonist that agonizes human P2Y13 at nanomolar levels, mouse P2Y13 and human P2Y12, induces platelet aggregation and morphological changes, and is indicated for neurological and cardiovascular disease studies.

MRS2179 is a competitive P2Y1 receptor antagonist with a Kb value of 100 nM and exhibits no appreciable activity at P2Y2, P2Y4, or P2Y6 receptors at concentrations up to 30 µM, nor at P2Y12 and P2Y13 receptors. MRS2179 inhibits ADP-induced platelet shape change and platelet aggregation in vitro, with a pA2 value of 6.55, and prolongs bleeding time in rats and mice relative to control groups. The receptor selectivity profile of MRS2179 supports its application in research focused on purinergic signaling, platelet biology, thrombosis-related mechanisms, and P2Y1 receptor-mediated cellular responses.

AGR-540 is a prodrug of AGR-529. AGR-540 has been shown to return plasma triglyceride concentrations to normal levels in mouse models. This effect may be attributed to an interaction of the molecule with A1 purinergic receptors of adipose tissue.

Clopidogrel is an antithrombic compound whose active metabolite is a selective, irreversible antagonist of the platelet purinergic P2Y12 receptor (IC50 = 100 nM). Clopidogrel inhibits ADP-induced platelet aggregation ex vivo and functions as a prodrug whereupon biotransformation to its active metabolite via CYP2C19 in the liver enables its anti-aggregating activity. Marketed under the name Plavix , clopidogrel in combination with aspirin has been shown to be beneficial in the prevention of vascular ischemic events for patients without deficiencies in CYP2C19-related metabolism.

Diadenosine pentaphosphate pentasodium is an endogenous vasoactive purine dinucleotide isolated from thrombocytes. Diadenosine pentaphosphate pentasodium is a component of secretory vesicles in platelets, chromaffin cells, Torpedo synaptic terminals, and brain synaptosomes. Diadenosine pentaphosphate pentasodium is therefore used in purinergic signaling research systems to investigate nucleotide-mediated vascular regulation, neurotransmission processes, and intracellular vesicular signaling mechanisms in physiological models.