P2X3 Receptor Antagonist

Aurintricarboxylic acid is a nanomolar-potency, allosteric antagonist with selectivity towards αβ-methylene-ATP-sensitive P2X1Rs and P2X3Rs, with IC₅₀s of 8.6 nM and 72.9 nM for rP2X1R and rP2X3R, respectively. Aurintricarboxylic acid is a potent anti-influenza agent by directly inhibiting the neuraminidase. Aurintricarboxylic acid is an inhibitor of topoisomerase II and apoptosis. Aurintricarboxylic acid is a selective inhibitor of the TWEAK-Fn14 signaling pathway. Aurintricarboxylic acid also acts as a cystathionine-lyase (CSE) inhibitor with an IC₅₀ of 0.6 μM. Aurintricarboxylic acid is a modifier of miRNAs that regulate miRNA function, with an IC₅₀ of 0.47 µM.

Gefapixant is an orally active and potent purinergic P2X3 receptor (P2X3R) antagonist, with IC₅₀ values of ~30 nM versus recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors. Gefapixant can be used for the research of chronic cough and knee osteoarthritis.

A-317491 is a potent, selective and non-nucleotide antagonist of P2X₃ and P2X_2/3 receptors, with K_is of 22, 22, 9, and 92 nM for hP2X₃, rP2X₃, hP2X_2/3, and rP2X_2/3, respectively. A-317491 is highly selective (IC50>10 μM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes. A-317491 reduces inflammatory and neuropathic pain by blocking P2X₃ and P2X_2/3 receptor-mediated calcium flux.

MK-3901 is a selective P2X3 receptor antagonist with an IC₅₀ of 24 nM. MK-3901 inhibits UGT1A1 (with an IC₅₀ of 1 μM) and CYP2C9 (with an IC₅₀ of 5.7 μM). MK-3901 activates PXR. MK-3901 induces hyperbilirubinemia. MK-3901 can be used for the research of inflammatory pain.

AF-353 (Ro-4) is a potent, selective and orally bioavailable P2X3/P2X2/3 receptor antagonist, with a pIC₅₀ of 8.0 for both human and rat P2X3, and with a pIC₅₀ of 7.3 for human P2X2/3.

TNP-ATP triethylammonium is a P2X receptor antagonist with an IC₅₀ of 0.010 μM for P2X₃ and an IC₅₀ of 0.062 μM for P2X_2/3. TNP-ATP triethylammonium acts as an inhibitor of CheA autophosphorylation, with a K_i of 0.7 µM. TNP-ATP triethylammonium blocks the functional activation of P2X_1-7 receptors. TNP-ATP triethylammonium attenuates hypoxia-induced IL-1β expression and release. TNP-ATP triethylammonium alleviates visceral pain, and improves hypoxia-induced cognitive impairment, insufficient myelination and neuroinflammation. Binding of TNP-ATP triethylammonium to CheA enhances the fluorescence of the TNP group. TNP-ATP triethylammonium can be used in studies related to visceral pain. NP-ATP triethylammonium can be used in studies related to hypoxia-induced insufficient myelination and cognitive decline.

Minodronic acid (YM-529) is an FPP synthase inhibitor with an IC₅₀ of 3 nM, and also an antagonist of P2X2/3 receptors with an IC₅₀ of 62.7 μM. Minodronic acid induces tumor cell apoptosis and inhibits cell growth. Minodronic acid also suppresses bone resorption. Minodronic acid can be used in research related to osteoporosis and cancer.

Eliapixant (BAY 1817080) is a potent and selective antagonist of P2X3 receptor, with an IC₅₀ of 8 nM. Eliapixant can be used for the research of refractory chronic cough.

NF279 is a selective P2X1 receptor antagonist and NTPDase inhibitor, with a P2X1 IC₅₀ value of 19 nM. NF279 suppresses GABA-evoked currents, reduces ATP-excited respiratory activity, alters hypoglossal nerve burst parameters, and blocks CXCR4, CCR5, CXCR3, and CXCR7-mediated calcium responses. NF279 arrests HIV-1 fusion downstream of CD4 binding, inhibits R5- and X4-tropic HIV-1 strains. NF279 can be used for the research of HIV-1 infection.

Opiranserin (VVZ-149) hydrochloride, a non-opioid and non-NSAID analgesic candidate, is a dual antagonist of glycine transporter type 2 (GlyT2) and serotonin receptor 2A (5HT2A), with IC₅₀s of 0.86 and 1.3 μM, respectively. Opiranserin hydrochloride shows antagonistic activity on rP2X3 (IC₅₀=0.87 μM). Opiranserin hydrochloride is development as an injectable agent for the treatment of postoperative pain.

A-317491 sodium salt hydrate is a potent, selective and non-nucleotide antagonist of P2X₃ and P2X_2/3 receptors, with K_is of 22, 22, 9, and 92 nM for hP2X₃, rP2X₃, hP2X_2/3, and rP2X_2/3, respectively. A-317491 sodium salt hydrate is highly selective (IC50>10 μM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes. A-317491 sodium salt hydrate reduces inflammatory and neuropathic pain by blocking P2X₃ and P2X_2/3 receptor-mediated calcium flux.

P2X3 antagonist 34 is a potent, selective and orally active P2X3 homotrimeric receptor antagonist with IC₅₀s of 25 nM, 92 nM and 126 nM for human P2X3, rat P2X3 and guinea pig P2X3 receptors, respectively. P2X3 antagonist 34 is less active against human, rat and guinea pig P2X2/3 heterotrimeric receptors. P2X3 antagonist 34 has strong anti-tussive effect.

Gefapixant citrate is an orally active and potent purinergic P2X3 receptor (P2X3R) antagonist, with IC₅₀ values of ~30 nM versus recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors. Gefapixant citrate can be used for the research of chronic cough and knee osteoarthritis.

Filapixant (BAY 1902607) is an orally active and selective P2X3 receptor antagonist. Filapixant is applicable to the research of refractory chronic cough.

RO-3 is a potent, and orally active P2X₃ and P2X_2/3 antagonist with pIC₅₀s of 5.9 and 7.0 for human homomultimeric P2X₃ and heteromultimeric P2X_2/3 receptors, respectively. RO-3 shows selectivity for P2X₃ and P2X_2/3 over all other functional homomultimeric P2X receptors (IC₅₀ >10 μM at P2X_1,2,4,5,7).

P2X3 antagonist 38 (compound 4) is a potent and orally active P2X3 antagonist with IC₅₀ values of 0.132, 0.165, 0.421 µM for hP2X3, rP2X3, gpP2X3, respectively.

Minodronic acid-d₄ (YM-529-d₄) is deuterium labeled Minodronic acid (HY-16322). Minodronic acid (YM-529) is an FPP synthase inhibitor with an IC₅₀ of 3 nM, and also an antagonist of P2X2/3 receptors with an IC₅₀ of 62.7 μM. Minodronic acid induces tumor cell apoptosis and inhibits cell growth. Minodronic acid also suppresses bone resorption. Minodronic acid can be used in research related to osteoporosis and cancer.

TNP-ATP is an antagonist of purinergic P2Y1, P2X3, and P2X2/3 receptors (IC₅₀ = 6, 0.9, and 7 nM, respectively, in HEK293 cells expressing human receptors). TNP-ATP reduces acetate-induced calcium flux in 1321N1 cells expressing P2X3 and P2X2/3 receptors (IC₅₀ = 100 and 62 nM, respectively). TNP-ATP dose-dependently attenuates acetate-induced abdominal contractions in a mouse visceral pain model (ED₅₀ = 6.35 µmol/kg)^[1][2].

TNP-GTP tetrasodium is a fluorescently labeled GTP (HY-113225) derivative. TNP-GTP tetrasodium can inhibit glutamate dehydrogenase (K_i = 2.7 μM). TNP-GTP tetrasodium is an antagonist of the purinergic P2X₂ and P2X_2/3 receptors with IC₅₀ values of 0.4 and 1.2 nM, respectively. TNP-GTP tetrasodium also inhibit rat soluble guanylyl cyclase (K_i = 11 nM).

Opiranserin (VVZ-149), a non-opioid and non-NSAID analgesic candidate, is a dual antagonist of glycine transporter type 2 (GlyT2) and serotonin receptor 2A (5HT2A), with IC₅₀s of 0.86 and 1.3 μM, respectively. Opiranserin shows antagonistic activity on rP2X3 (IC₅₀=0.87 μM). Opiranserin is development as an injectable agent for the treatment of postoperative pain.