p2x2

A-317491 (ABT 202) is a non-nucleotide P2X3 ( Ki: 22 nM) and P2X2/3 receptor (Ki: 9 nM) antagonist, which inhibits calcium flux mediated by the receptors.

P2X3 antagonist 34, a potent, selective, and orally active antagonist, targets the P2X3 homotrimeric receptor, exhibiting IC50s of 25 nM, 92 nM, and 126 nM for human, rat, and guinea pig P2X3 receptors respectively. It shows reduced activity against P2X2/3 heterotrimeric receptors across human, rat, and guinea pig models. Notably, this compound demonstrates a significant anti-tussive effect without altering taste[1].

Reactive Blue 4 analog disodium is an analog of Reactive Blue 4 exhibiting inhibitory activity against P2X2 (IC50 = 0.3–1 µM).

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.

P2X2/3 Modulator-1 (Compound 46) serves as a modulator of P2X2/3 receptors and has applications in researching pain, central nervous system disorders, and inflammation [1].

Minodronic acid(YM-529) is a P2X2/3 receptor antagonist with anticancer activity, directly or indirectly inhibiting the proliferation of cancer cells and inducing apoptosis. Minodronic acid has been shown to inhibit the metastasis of various types of cancer cells.Minodronic-acid has been used in the study of osteoporosis.

BzATP triethylammonium salt is a P2X7 receptor agonist.

Adenosine 5'-diphosphate (ADP) is a naturally occurring nucleotide derived from the dephosphorylation of ATP. Adenosine 5'-diphosphate is essential for cellular metabolism and induces platelet aggregation.

dual P2X3 and P2X2/3 antagonist

Gefapixant (AF219) is a P2X3 receptor (P2X3R) antagonist with IC50 of ~30 nM at recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors.

Camlipixant (BLU-5937) is an orally active purine P2X3 receptor antagonist that is potent, selective and competitive. camlipixant has an IC50 of 25 nM for the hP2X3 homotrimer. camlipixant can be used for the treatment of respiratory disorders and Camlipixant has a strong cough suppressant effect.

PPADS is a P2 receptor antagonist with IC50 values of 68 nM (P2X1) and 214 nM (P2X3). This compound functions as an ATP (nucleotide) analog, competing for binding sites on the P2 receptors with ATP. Additionally, PPADS acts as a reversible competitive antagonist of the NAADP receptor. It is capable of reversing hyperalgesia, and it diminishes the enhanced NO/NOS signaling and IL-1β production in both peripheral and central steps of the nervous system.

BAY-1797 is an orally active and selective P2X4 antagonist (IC50: 211 nM against human P2X4) with anti-nociceptive and anti-inflammatory effects. BAY-1797 displays no or very weak activity on the other P2X ion channels.

AF-353 (Ro-4), an effective and orally bioavailable antagonist of the P2X3/P2X2/3 receptor, inhibits human and rat P2X3 (pIC50= 8.0).

A-317491 sodium salt hydrate is a non-nucleotide P2X3 and P2X2/3 receptor antagonist that inhibits receptor-mediated calcium flux.

α,β-Methylene ATP trisodium, a phosphonate analog of ATP, is a selective P2X agonist that induces enhanced contraction of UBSM. α,β-Methylene ATP trisodium inhibits P2X1 and P2X3, but is inactive against P2X2, 4 and 7.

NF449 is a potent antagonist of the P2X1 receptor, displaying IC50 values of 0.28 nM, 0.69 nM, and 120 nM for rP2X1, rP2X1+5, and P2X2+3, respectively. It acts selectively against Gsα G proteins (G Protein). NF449 inhibits the binding rate of GTP[γS] to Gsα-s, suppresses the stimulation of adenylate cyclase activity, and blocks the coupling of β-adrenergic receptors with Gs.

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.

2-Methylthio-ATP tetrasodium (2-MeS-ATP tetrasodium) is a non-specific P2 receptor agonist, which can activate P2X2 and P2Y1 receptors and mimic the physiological effects of ATP by binding to P2 receptors, and is widely used in the study of cell signaling and metabolic processes. In addition, 2-Methylthio-ATP tetrasodium induces non-competitive inhibition of ADP-induced platelet aggregation in human.

P2X3 and P2X2/3 receptor antagonist

PSB-1011 is a selective and competitive inhibitor of the rat P2X2 receptor (Ki = 79 nM).

α,β-Methylene ATP dilithium, a phosphonic analog of ATP, serves as a ligand for P2X3 and P2X7 receptors. It is a potent agonist specifically targeting P2X1 and P2X3 receptors while exerting negligible activity on P2X2, P2X4, P2X5, P2X6, and P2X7 receptors.

Sivopixant (S-600918) (S-600918) is a potent and selective antagonist of P2X3 receptor (P2X3 IC 50 =4.2 nM; P2X2/3 IC 50 =1100 nM). Sivopixant shows strong analgesic effect .

RO3 is a selective antagonist of homomeric P2X3 and heteromeric P2X2/3 receptor