P2X Receptor Antagonist

NF449 octasodium is a highly potent P2X₁ receptor antagonist, with IC₅₀s of 0.28, 0.69, and 120 nM for rP2X₁, rP2X₁₊₅, P2X₂₊₃, respectively. NF449 octasodium is a G_sα-selective G Protein antagonist. NF449 octasodium suppresses the rate of GTP[γS] binding to G_sα-s, inhibits the stimulation of adenylyl cyclase activity, and blocks the coupling of β-adrenergic receptors to G_s.

A-740003 is a potent, selective and competitive P2X7 receptor antagonist with IC₅₀ values are 18 and 40 nM for rat and human P2X7 receptors, respectively.

A 438079 is a potent, and selective P2X₇ receptor antagonist with pIC₅₀ of 6.9.

PSB-10211 is a P2X2 receptor antagonist with an IC₅₀ of 0.086 μM against rat P2X2 receptors. PSB-10211 inhibits ATP-mediated currents of rat P2X2 receptors expressed in Xenopus oocytes. PSB-10211 can be used in studies related to pain and urinary incontinence.

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.

5-BDBD, a potent and selective P2X4 receptor antagonist, inhibits rP2X4R-mediated currents, with an IC₅₀ of 0.75 μM. 5-BDBD completely blocks the basal and acute hyperalgesia induced by nitroglycerin (NTG).

PPADS tetrasodiuma is a non-selective P2X receptor antagonist. PPADS tetrasodiuma blocks recombinant P2X1, -2, -3, -5 with IC₅₀s ranging from 1 to 2.6 μM. PPADS tetrasodiuma blocks native P2Y2-like (IC₅₀~0.9 mM) and recombinant P2Y4 (IC₅₀~15 mM) receptors. PPADS tetrasodiuma is an inhibitor of the reverse mode of the Na/Ca²⁺ exchanger in guinea pig airway smooth muscle.

KN-62 is a selective and reversible inhibitor of calmodulin-dependent protein kinase II (CaMK-II) with a K_i of 0.9 μM for rat brain CaMK-II. KN-62 directly binds to the calmodulin binding site of CaMK-II. KN-62 displays noncompetitive antagonism at P2X₇ receptors in HEK293 cells, with an IC₅₀ value of approximately 15 nM.

BAY-1797, a chemical probe, is a potent, orally active, and selective P2X4 antagonist, with an IC₅₀ of 211 nM against human P2X4. BAY-1797 displays no or very weak activity on the other P2X ion channels. BAY-1797 shows anti-nociceptive and anti-inflammatory effects.

A 438079 (hydrochloride) is a potent, and selective P2X₇ receptor antagonist with pIC₅₀ of 6.9.

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.

JNJ-47965567 is a centrally permeable, high-affinity, selective P2X7 antagonist, with pK_is of 7.9 and 8.7 for human and rat P2X7, respectively. JNJ-47965567 can be used to probe the role of central P2X7 in rodent models of CNS pathophysiology.

Camlipixant (BLU-5937) a potent, selective, non-competitive and orally active P2X3 homotrimeric receptor antagonist with an IC₅₀ of 25 nM against hP2X3 homotrimeric. Camlipixant shows potent anti-tussive effect and no taste alteration. Camlipixant can be used for the research of unexplained, refractory chronic cough.

AZ10606120 dihydrochloride is a selective, high affinity antagonist for P2X7 receptor (P2X7R) at human and rat with an IC₅₀ of about 10 nM. AZ10606120 dihydrochloride is little or no effect at other P2XR subtypes. AZ10606120 dihydrochloride has anti-depressant effects and reduces tumour growth.

A-804598 is a BBB penetrant, competitive and selective P2X7 receptor antagonist with IC₅₀s of 9 nM, 10 nM and 11 nM for mouse, rat and human P2X7 receptors, respectively.

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.

BX430 is a potent and selective noncompetitive allosteric human P2X4 receptor channels antagonist with an IC₅₀ of 0.54 μM. BX430 has species specificity. BX430 is used for chronic pain and cardiovascular disease.

Tricarbonyldichlororuthenium(II) dimer (CORM-2) is a CO-releasing molecule. Tricarbonyldichlororuthenium(II) dimer exhibits anti-inflammatory, antioxidant, and gastric mucosa-protective activities. Additionally, Tricarbonyldichlororuthenium(II) dimer has CO-independent functional effects on multiple potassium channels.

JNJ-55308942 is a high-affinity, selective, brain-penetrant P2X7 functional antagonist (hP2X7: IC₅₀=10 nM, K_i=7.1 nM; rP2X7: IC₅₀=15 nM, K_i=2.9 nM). JNJ-55308942 is orally bioavailable, binds to brain P2X7 and blocks IL-1β release from adult rodent brain.

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.