purinergic

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

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.

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.

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.

ITH15004 is a non-nucleotide antagonist of the purinergic P2X7receptor (IC50= 9 μM in HEK293 cells expressing the human receptor).1It inhibits ATP-induced currents inX. laevisoocytes expressing the human P2X7receptor when used at a concentration of 100 μM. ITH15004 (1 μM) decreases IL-1β release from LPS-primed, ATP-stimulated isolated mouse peritoneal macrophages. It has high permeability in a parallel artificial membrane permeability assay (PAMPA). 1.Calzaferri, F., Narros-Fernández, P., de Pascual, R., et al.Synthesis and pharmacological evaluation of novel non-nucleotide purine derivatives as P2X7 antagonists for the treatment of neuroinflammationJ. Med. Chem.64(4)2272-2290(2021)

8-Bromo-ATP (8-Bromoadenosine 5'-triphosphate) is a purinergic P2X receptor agonist and ATP analogue that exhibits cytotoxicity towards multiple myeloma cells, with an IC50 of 23.1 μM.

JNJ-47965567 (JNJ-479655) is a selective antagonist of the purinergic receptor P2X subtype 7 (P2X7), a ligand-gated ion channel(with pKis of 7.9 and 8.7 for human and rat P2X7, respectively).

P2X7 receptor antagonist-1 is a purinergic P2X7 receptor antagonist with anti-neuroinflammatory effects.

BMS-870145 is a potent and selective P2Y1 purinergic receptor antagonist..

KF 20274 is an adenosine A1 antagonist; purinergic receptor antagonist.

EVT-401 (P2X7 receptor antagonist-1), a purinergic P2X7 receptor antagonist, demonstrates efficacy in combating neuroinflammation [1].

UDP-β-S, serving as a specific agonist for the purinergic P2Y6 receptor, effectively promotes inositol phosphate accumulation in 1321N1 cells containing P2Y6 receptors, with an EC50 value of 28 nM. This selectivity is evident when compared to its effects on cells expressing P2Y1, P2Y2, or P2Y4 receptors, where a concentration of 10 µM is used. Additionally, at a concentration of 1 µM, UDP-β-S stimulates DNA synthesis in isolated rat aorta smooth muscle cells.

Rp-Adenosine-5'-O-(1-thiotriphosphate) (Rp-ATP-α-S), a sulfur-containing nucleotide derivative isomer and a purinergic P2Y1 receptor agonist, promotes calcium mobilization in HEK293 cells expressing the human P2Y1 receptor (EC50 = 75 nM). This compound exhibits binding affinity to washed isolated human platelets (Ki = 156 nM) and attenuates ADP-induced aggregation in human platelet-rich plasma (PRP; pA2 = 4.74), as well as inhibits cAMP production triggered by prostaglandin E1 (PGE1) in human PRP (pA2 = 5.26). Furthermore, it triggers relaxation in carbamoylcholine-constricted guinea pig taenia coli strips (EC50 = 56 nM). Rp-ATP-α-S also contributes to the synthesis of cyclic dinucleotides, recognized by bacterial riboswitches.

Sp-Adenosine-5'-O-(1-thiotriphosphate) (Sp-ATP-α-S), an isomer of the ATP-α-S sulfur-containing nucleotide derivative and a purinergic P2Y1 receptor agonist, effectively increases calcium mobilization in HEK293 cells harboring the P2Y1 receptor with an EC50 of 9.4 nM for the human receptor. It also inhibits ADP-induced human isolated platelet aggregation with a Ki value of 4 μM and prompts relaxation in carbamoylcholine-tightened guinea pig taenia coli, achieving an EC50 of 426 nM.