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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 484

Nomenclature: P2X7

Family: P2X receptors

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 595 12q24.31 P2RX7 purinergic receptor P2X 7 15,80
Mouse 2 595 5 F P2rx7 purinergic receptor P2X, ligand-gated ion channel, 7 20
Rat 2 595 12q16 P2rx7 purinergic receptor P2X 7 95
Previous and Unofficial Names Click here for help
P2X purinoceptor 7 | P2Z receptor | P2X7 receptor | purinergic receptor P2X, ligand gated ion channel, 7 | purinergic receptor P2X
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands Click here for help

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BzATP Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.3 pEC50 31
pEC50 5.3 (EC50 4.677x10-6 M) [31]
Description: Measuring agonist-stimulated P2X7 receptor-mediated changes in intracellular calcium concentration.
BzATP Small molecule or natural product Rn Agonist 5.0 pEC50 31
pEC50 5.0 (EC50 1x10-5 M) [31]
Description: Measuring agonist-stimulated P2X7 receptor-mediated changes in intracellular calcium concentration.
BzATP Small molecule or natural product Mm Agonist 4.0 pEC50 31
pEC50 4.0 (EC50 1x10-4 M) [31]
Description: Measuring agonist-stimulated P2X7 receptor-mediated changes in intracellular calcium concentration.
ATP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 3.1 pEC50 54
pEC50 3.1 (EC50 7.8x10-4 M) [54]
View species-specific agonist tables
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AZ11657312 (salt free) Small molecule or natural product Immunopharmacology Ligand Rn Antagonist 7.8 pA2 7
pA2 7.8 [7]
decavanadate Click here for species-specific activity table Hs Antagonist 7.4 pA2 69
pA2 7.4 pA2 = 7.4 [69]
AZ11657312 (salt free) Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Antagonist 6.1 pA2 7
pA2 6.1 [7]
AZ10606120 Small molecule or natural product Primary target of this compound Hs Antagonist 8.9 pKd 66
pKd 8.9 (Kd 1.4x10-9 M) [66]
Description: Measuring binding of [3H]-AZ10606120 to human P2X7 receptors
AZ10606120 Small molecule or natural product Rn Antagonist 8.7 pKd 66
pKd 8.7 (Kd 1.9x10-9 M) [66]
Description: Measuring binding of [3H]-AZ10606120 to rat P2X7 receptors
JNJ-47965567 Small molecule or natural product Ligand has a PDB structure Hs Antagonist 7.9 pKi 11
pKi 7.9 (Ki 1.26x10-8 M) [11]
JNJ-47965567 Small molecule or natural product Ligand has a PDB structure Hs Antagonist 8.3 pIC50 11
pIC50 8.3 (IC50 5x10-9 M) [11]
Description: Measuring antagonism of BzATP induced calcium flux.
A804598 Small molecule or natural product Hs Antagonist ~8.0 pIC50
pIC50 ~8.0 (IC50 ~1x10-8 M)
brilliant blue G Small molecule or natural product Hs Antagonist ~8.0 pIC50 55
pIC50 ~8.0 (IC50 ~1x10-8 M) [55]
A839977 Small molecule or natural product Hs Antagonist ~7.7 pIC50 30-31,52
pIC50 ~7.7 (IC50 ~2x10-8 M) [30-31,52]
A740003 Small molecule or natural product Hs Antagonist 7.4 pIC50 53
pIC50 7.4 (IC50 4x10-8 M) [53]
GSK1482160 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 6.9 pIC50 51
pIC50 6.9 (IC50 1.193x10-7 M) [51]
A438079 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist ~6.9 pIC50 30
pIC50 ~6.9 (IC50 ~1.25x10-7 M) [30]
compound 16i [PMID: 31525963] Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 6.6 pIC50 51
pIC50 6.6 (IC50 2.29x10-7 M) [51]
GSK1370319A Small molecule or natural product Hs Antagonist 6.3 pIC50 51
pIC50 6.3 (IC50 4.74x10-7 M) [51]
ITH15004 Small molecule or natural product Hs Antagonist 5.1 pIC50 17
pIC50 5.1 (IC50 9x10-6 M) [17]
oxidised ATP Small molecule or natural product Mm Irreversible inhibition 3.5 pIC50 70
pIC50 3.5 (IC50 3.162x10-4 M) [70]
PF-04905428 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Antagonist - - 29,32
View species-specific antagonist tables
Antagonist Comments
Oxidized ATP is an irreversible antagonist of P2X7 [70].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
GSK1482160 Small molecule or natural product Immunopharmacology Ligand Hs Binding 8.9 pKd - no 98
pKd 8.9 (Kd 1.15x10-9 M) [98]
Not voltage dependent
Description: Binding affinity determined in a radioligand binding assay.
GSK1482160 Small molecule or natural product Immunopharmacology Ligand Hs Negative 8.5 pIC50 - no 1
pIC50 8.5 (IC50 3.16x10-9 M) Reversible negative allosteric modulator. [1]
Not voltage dependent
GSK1482160 Small molecule or natural product Immunopharmacology Ligand Rn Negative 6.5 pIC50 - no 1
pIC50 6.5 (IC50 3.16x10-7 M) Reversible negative allosteric modulator [1]
Not voltage dependent
chelerythrine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Negative 5.3 pIC50 - no 85
pIC50 5.3 (IC50 5.6x10-6 M) [85]
Not voltage dependent
Description: Inhibition of ATP-induced 86Rb+ (K+) efflux in human B-lymphocytes
ivermectin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Positive - - - no 75
Not voltage dependent
AZ11645373 Small molecule or natural product Hs Negative - - - no 68,93
Not voltage dependent
KN62 Small molecule or natural product Click here for species-specific activity table Hs Negative - - - no 41,85
Not voltage dependent
LL-37 {Sp: Human} Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Positive - - - no 99
Not voltage dependent
clemastine Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Positive - - - no 74
Not voltage dependent
AZ10606120 Small molecule or natural product Primary target of this compound Hs Negative - - - no 66
Not voltage dependent
Not voltage dependent
GW791343 Small molecule or natural product Ligand has a PDB structure Hs Negative - - - no 66-67
Not voltage dependent
GW791343 Small molecule or natural product Ligand has a PDB structure Rn Positive - - - no 66-67
Not voltage dependent
polymyxin B Peptide Approved drug Hs Positive - - - no 37
Not voltage dependent
View species-specific allosteric modulator tables
Allosteric Modulator Comments
Effects of the allosteric regulators at P2X7 receptors are species-dependent. See Michel et al. (2008) [67] for an explanation.
No affinity data has been published quantifying the complex interaction of GW791343 with the P2X7 receptor. We have included the interaction in the table above based on extensive experimental evidence provided in [66] and [67]. Polymyxin B is a P2X7 receptor PAM [37].
Immunopharmacology Comments
The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [63,81]. In human mast cells P2X7 receptor activation causes degranulation and inflammatory mediator release [102], and in mouse mast cells induces IL-6 and TNF-α production [63]. Studies in mice suggest that ATP released from damaged airway tissue engages the P2X7 receptor/pannexin-1 axis, leading to IL-1β maturation and pulmonary fibrosis.[82]. P2X7 receptor antagonism has also been posited as a potential pharmaceutical intervention to treat the salivary gland inflammation and sequelae of Sjögrens syndrome [60].
Cell Type Associations
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
Comment:  P2XR7 activity is involved in DC priming.
References:  100
Immuno Cell Type:  T cells
Comment:  P2RX7 is expressed by most immune cells. It elicits an immune response when activated by extracellular ATP that is released by infected or injured cells. P2RX7 expressed on T cells is involved in proliferation, cytokine production, Th17 and T follicular helper cell differentiation and inhibition of Treg differentiation.
References:  3,28,100
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Comment:  Human B cells express all P2 receptor subtypes.
References:  78
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Tissue Distribution Click here for help
Brain, lung, prostate, leukocytes
Expression level:  Medium
Species:  Human
Technique:  Northern blot
References:  57,80
Fibroblasts; dendritic cells, osteoblasts, B lymphocytes, T lymphocytes, keratinocytes, erithrocytes, microglia
Expression level:  Medium
Species:  Human
Technique:  RT-PCR, Western blot, flow cytometry, immunohistochemistry, immunofluorescence
References:  10,14,42,44,88-90,104-105
Bladder, astrocytes
Expression level:  Low
Species:  Human
Technique:  RT-PCR
References:  72,76
Heart, liver, skeletal muscle, pancreas, thymus, tonsils, monocytes, macrophages, osteoclasts
Expression level:  High
Species:  Human
Technique:  Immunohistochemistry, Northern blot; flow cytometry; RT-PCR
References:  14,35,42,80
Bone marrow, macrophages, granulocytes, B lymphocytes, mast cells, submandibular glands, lung, microglia, Schwann cells, kidney, osteoclasts, osteoblasts, liver
Expression level:  High
Species:  Mouse
Technique:  In situ hybridisation, RT-PCR, Western blot, Immunofluorescence
References:  20,22-23,33,36,45,48,59,86
Bone marrow, macrophages, osteoclasts
Expression level:  High
Species:  Rat
Technique:  in situ hybridization
References:  22,71
New born brain, lung, spleen, bone marrow, spleen, salivary glands, testis, brain (ependyma,neurons from olfactory nucleus, cerebral cortex, piriform cortex, lateral septal nucleus, hippocampal pyramidal cells, oligodendrocytes, microglia), retina, parotid gland, lacrimal glands, pancreas, liver.
Expression level:  High
Species:  Rat
Technique:  in situ hybridization, RT-PCR, Northern Blot, Western blot, Immunofluorescence, Immunohistochemistry
References:  13,22,24,33,39,50,94,97,106
Physiological Consequences of Altering Gene Expression Click here for help
Increased proliferation.
Species:  Human
Tissue:  B lymphoblastoid cells.
Technique:  Transfection.
References:  8
Decreased proliferation
Species:  Mouse
Tissue:  microglia
Technique:  RNAi
References:  12
Reduced experimental arthritis, defective bone homeostasis; reduced neuropathic pain; reduced autoimmune hepatitis, reduced inflammation and fibrosis following ureteral obstruction, reduced experimental glomerulonephritis, defective wound healing, defective experimental encephalitis; reduced smoke-induced lung inflammation
Species:  Mouse
Tissue:  joint tissue, long bones, nervous system; liver, kidney, cornea, brain, lung
Technique:  Knock-out
References:  19,43,58-59,61,64-65,84,96
Anti-depressant-like behaviour, spatial memory impairment
Species:  Mouse
Tissue:  brain
Technique:  Knock-out
References:  9,62
Defective IL-1 release; defective intraphagosomal killing
Species:  Mouse
Tissue:  macrophages, microglia
Technique:  Knock-out
References:  34,38,83,91
Reduced long term potentiation and allodynia
Species:  Rat
Tissue:  spinal cord
Technique:  RNAi
References:  21,92
Gene Expression and Pathophysiology Click here for help
Tissue or cell type:  Kidney
Pathophysiology:  Experimental diabetes/hypertension
Species:  Mouse
Technique:  Immunohistochemistry, Western blotting
References:  101
Tissue or cell type:  B lymphocytes
Pathophysiology:  Chronic lymphocytic leukemia
Species:  Human
Technique:  RT-PCR, Western blot
References:  4
Tissue or cell type:  Kidney
Pathophysiology:  Autosomal recessive polycystic kidney disease
Species:  Human
Technique:  Immunocytochemistry
References:  49
Tissue or cell type:  Retina
Pathophysiology:  Retinal degeneration
Species:  Mouse
Technique:  RT-PCR, immunohistochemistry
References:  40
Tissue or cell type:  Neuroblastoma cells
Pathophysiology:  Carcinomas
Species:  Human
Technique:  Immunohistochemistry
References:  79
Tissue or cell type:  Spinal cord
Pathophysiology:  Multiple sclerosis, Amiotrophic lateral sclerosis
Species:  Human
Technique:  Immunocytochemistry, Western blotting
References:  104
Tissue or cell type:  Microglia
Pathophysiology:  Mouse model of Alzheimer's disease
Species:  Mouse
Technique:  Immunofluorescence
References:  77
Tissue or cell type:  Melanoma, colon carcinoma.
Pathophysiology:  Cancer.
Species:  Mouse
Technique:  Immunocytochemistry, RT-PCR.
References:  5
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Single nucleotide substitution causing gain-of-function.
Amino acid change:  H155Y
Nucleotide change:  489C>T
SNP accession: 
References:  16
Type:  Splice variant
Species:  Human
Description:  P2X7B: C-terminally truncated form of the full length P2X7A. This variant is due to transcription of the intron between exons 10 and 11. This inclusion introduces a new stop codon and modifies the last C-terminal 18 amino acids. GenBank accessions are AY847298 (nucleotide) and AAX82087.1 (protein).
Amino acids:  364
References:  2,18
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Nucleotide substitution causing loss-of-function.
Amino acid change:  E496A
Nucleotide change:  151 A>C
SNP accession: 
References:  47
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Nucleotide substitution causing loss-of-function.
Amino acid change:  I568N
Nucleotide change:  1729T>A
SNP accession: 
References:  103
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Nucleotide substitution causing loss-of-function.
Amino acid change:  R307Q
Nucleotide change:  946G>A
SNP accession: 
References:  46
Type:  Single nucleotide polymorphism
Species:  Mouse
Description:  Allelic mutation in the COOH tail of C57BL/6 and DBA mice decreases sensitivity to ATP
References:  6
Type:  Splice variant
Species:  Mouse
Description:  Alternative transmembrane domain 1. This variant escapes gene inactivation in P2X7 knock-out mice
Amino acids:  592
Nucleotide accession: 
Protein accession: 
References:  73
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Splice site mutation at position +1 in intron 1, SNP 151+1g>t (rs35933842:- null allele)
References:  87
General Comments
The role of P2X7 receptor in cancer is discussed in [25-27]. The crystal structure of the truncated (lacking 240 C-terminal residues) P2X7 receptor from giant panda (Ailuropoda melanoleuca) has been resolved. This has allowed identification of the mechanism of action of several widely used antagonists [56]. Recent crystallographic data suggest that three antagonists (A740003, A804598, JNJ-47965567) previously classified as competitive inhibitors are in fact allosteric, non competitive, inhibitors [56].


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2. Adinolfi E, Cirillo M, Woltersdorf R, Falzoni S, Chiozzi P, Pellegatti P, Callegari MG, Sandonà D, Markwardt F, Schmalzing G et al.. (2010) Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J, 24 (9): 3393-404. [PMID:20453110]

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7. AstraZeneca. AZ11657312. Accessed on 12/09/2014. Modified on 12/09/2014.,

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16. Cabrini G, Falzoni S, Forchap SL, Pellegatti P, Balboni A, Agostini P, Cuneo A, Castoldi G, Baricordi OR, Di Virgilio F. (2005) A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes. J Immunol, 175 (1): 82-9. [PMID:15972634]

17. Calzaferri F, Narros-Fernández P, de Pascual R, de Diego AMG, Nicke A, Egea J, García AG, de Los Ríos C. (2021) Synthesis and Pharmacological Evaluation of Novel Non-nucleotide Purine Derivatives as P2X7 Antagonists for the Treatment of Neuroinflammation. J Med Chem, 64 (4): 2272-2290. DOI: 10.1021/acs.jmedchem.0c02145 [PMID:33560845]

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37. Ferrari D, Pizzirani C, Adinolfi E, Forchap S, Sitta B, Turchet L, Falzoni S, Minelli M, Baricordi R, Di Virgilio F. (2004) The antibiotic polymyxin B modulates P2X7 receptor function. J Immunol, 173 (7): 4652-60. [PMID:15383600]

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