General Information of Drug Therapeutic Target (DTT) (ID: TT473XN)

DTT Name P2X purinoceptor 7 (P2RX7)
Synonyms Purinergic receptor 7; P2Z receptor; P2X7; Adenosine P2X7 receptor; ATP receptor
Gene Name P2RX7
DTT Type
Clinical trial target
[1]
BioChemical Class
ATP-gated P2X receptor cation channel
UniProt ID
P2RX7_HUMAN
TTD ID
T63414
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MPACCSCSDVFQYETNKVTRIQSMNYGTIKWFFHVIIFSYVCFALVSDKLYQRKEPVISS
VHTKVKGIAEVKEEIVENGVKKLVHSVFDTADYTFPLQGNSFFVMTNFLKTEGQEQRLCP
EYPTRRTLCSSDRGCKKGWMDPQSKGIQTGRCVVYEGNQKTCEVSAWCPIEAVEEAPRPA
LLNSAENFTVLIKNNIDFPGHNYTTRNILPGLNITCTFHKTQNPQCPIFRLGDIFRETGD
NFSDVAIQGGIMGIEIYWDCNLDRWFHHCRPKYSFRRLDDKTTNVSLYPGYNFRYAKYYK
ENNVEKRTLIKVFGIRFDILVFGTGGKFDIIQLVVYIGSTLSYFGLAAVFIDFLIDTYSS
NCCRSHIYPWCKCCQPCVVNEYYYRKKCESIVEPKPTLKYVSFVDESHIRMVNQQLLGRS
LQDVKGQEVPRPAMDFTDLSRLPLALHDTPPIPGQPEEIQLLRKEATPRSRDSPVWCQCG
SCLPSQLPESHRCLEELCCRKKPGACITTSELFRKLVLSRHVLQFLLLYQEPLLALDVDS
TNSRLRHCAYRCYATWRFGSQDMADFAILPSCCRWRIRKEFPKSEGQYSGFKSPY
Function
Responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells. In the absence of its natural ligand, ATP, functions as a scavenger receptor in the recognition and engulfment of apoptotic cells. Receptor for ATP that acts as a ligand-gated ion channel.
KEGG Pathway
Calcium signaling pathway (hsa04020 )
Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway
The NLRP3 inflammasome (R-HSA-844456 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
10 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CE-224535 DMFCLT6 Arthralgia ME82 Phase 2/3 [1]
AZD9056 DMJGYPK Chronic obstructive pulmonary disease CA22 Phase 2 [2]
LY3857210 DMZO2V2 Pain MG30-MG3Z Phase 2 [3]
BIL010t DMV1EA9 Alzheimer disease 8A20 Phase 1/2 [4]
EVT 401 DMOG8IE Rheumatoid arthritis FA20 Phase 1 [5]
GSK1482160 DMWDQOV Pain MG30-MG3Z Phase 1 [6]
JNJ-54175446 DMQ5ZVK Major depressive disorder 6A70.3 Phase 1 [7]
JNJ-55308942 DM0QZJX Anhedonia MB24.2 Phase 1 [4]
SGM-1019 DMDAHEL Inflammatory bowel disease DD72 Phase 1 [8]
JNJ-479655 DMDU6GN Alzheimer disease 8A20 Clinical trial [9]
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⏷ Show the Full List of 10 Clinical Trial Drug(s)
34 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Aminobenzoxazole analog 1 DM1RQIU N. A. N. A. Patented [10]
Benzamide derivative 12 DMS527F N. A. N. A. Patented [10]
Benzamide derivative 13 DMYSH9J N. A. N. A. Patented [10]
Bicyclic heteroaryl amide derivative 1 DMOFI09 N. A. N. A. Patented [10]
Bicyclic heteroaryl amide derivative 2 DM69HL5 N. A. N. A. Patented [10]
Bicyclic heteroaryl amide derivative 3 DM0OYCX N. A. N. A. Patented [10]
Chlorobenzamide derivative 1 DMR39ZY N. A. N. A. Patented [10]
Chlorobenzamide derivative 2 DMKS7O3 N. A. N. A. Patented [10]
Dihydroisoquinoline carboxamide analog 1 DM5UPGZ N. A. N. A. Patented [10]
Fluorophenyl-substituted heterocyclic amide analog 1 DMTS8O9 N. A. N. A. Patented [10]
Fused triazoloamino-phenyl analog 1 DM4Z72S N. A. N. A. Patented [10]
Heterocyclic-fused piperazine derivative 1 DMEGK3Q N. A. N. A. Patented [10]
Imidazolidine derivative 1 DMECJDM N. A. N. A. Patented [10]
Indole carboxamide derivative 1 DMLHGC9 N. A. N. A. Patented [10]
Isoindole 1,3-dione analog 1 DMWTU8X N. A. N. A. Patented [10]
Isothiazolidine derivative 1 DMLSUH3 N. A. N. A. Patented [10]
Piperazine derivative 6 DMDL3A5 N. A. N. A. Patented [10]
Piperidinone derivative 1 DMAM50X N. A. N. A. Patented [10]
PMID27724045-Compound-14 DMTJ0LB N. A. N. A. Patented [10]
PMID27724045-Compound-15 DMVN5BD N. A. N. A. Patented [10]
PMID27724045-Compound-17 DM4W72V N. A. N. A. Patented [10]
PMID27724045-Compound-19 DMVDBHT N. A. N. A. Patented [10]
PMID27724045-Compound-29 DMKTQX8 N. A. N. A. Patented [10]
PMID27724045-Compound-33 DMOS7ZP N. A. N. A. Patented [10]
Pyridazinone derivative 1 DMF7MEB N. A. N. A. Patented [10]
Quinoline derivative 10 DM6GSCV N. A. N. A. Patented [10]
Quinoline derivative 11 DMH02JL N. A. N. A. Patented [10]
Quinoline derivative 12 DM9FXE7 N. A. N. A. Patented [10]
Quinoline derivative 13 DMAH4P8 N. A. N. A. Patented [10]
Tetrazole derivative 1 DM1AGSD N. A. N. A. Patented [10]
Thiazole derivative 5 DMESAUL N. A. N. A. Patented [10]
Thiazole-fused cycloalkyl carboxamide derivative 1 DMCPV0D N. A. N. A. Patented [10]
Triazole derivative 2 DM7KNXH N. A. N. A. Patented [10]
Triazolo-pyrazinone derivative 1 DM1KHGY N. A. N. A. Patented [10]
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⏷ Show the Full List of 34 Patented Agent(s)
14 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
A-740003 DMI7J1L Discovery agent N.A. Investigative [11]
A438079 DMUBM8X Discovery agent N.A. Investigative [12]
A804598 DMLC7HE N. A. N. A. Investigative [13]
A839977 DMPXKOE Discovery agent N.A. Investigative [14]
AFC-5128 DM65TUP Autoimmune diabetes 5A10 Investigative [13]
AZ-11657312 DMRUA0Y Inflammation 1A00-CA43.1 Investigative [13]
AZ11645373 DMDRXCP Discovery agent N.A. Investigative [15]
AZ11657312 (salt free) DMVX8LO Discovery agent N.A. Investigative [13]
chelerythrine DMCP1G9 Discovery agent N.A. Investigative [16]
decavanadate DMLT1N3 Discovery agent N.A. Investigative [17]
ISOPPADS DMWI0M8 Discovery agent N.A. Investigative [18]
KN-62 DMLZ89P Discovery agent N.A. Investigative [19]
STYLISSADINE A DMO9VWJ Discovery agent N.A. Investigative [11]
STYLISSADINE B DMNAYEP Discovery agent N.A. Investigative [11]
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⏷ Show the Full List of 14 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Alzheimer's disease 8A00.0 Entorhinal cortex 1.11E-06 0.37 0.49
Rheumatoid arthritis FA20 Synovial tissue 1.71E-02 1.08 1.25
Chronic obstructive pulmonary disease CA23 Lung tissue 3.17E-01 -0.1 -0.22
Chronic obstructive pulmonary disease CA23 Small airway epithelium 5.97E-02 0.16 0.37
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References

1 Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate. J Rheumatol. 2012 Apr;39(4):720-7.
2 Clinical pipeline report, company report or official report of AstraZeneca (2009).
3 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
4 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
5 Molecular and functional properties of P2X receptors ecent progress and persisting challenges. Purinergic Signal. 2012 September; 8(3): 375-417.
6 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9 Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br J Pharmacol. 2013 Oct;170(3):624-40.
10 P2X7 receptor antagonists: a patent review (2010-2015).Expert Opin Ther Pat. 2017 Mar;27(3):257-267.
11 Purinergic P2X(7) receptor antagonists: Chemistry and fundamentals of biological screening. Bioorg Med Chem. 2009 Jul 15;17(14):4861-5.
12 Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states. Br J Pharmacol. 2007 Jul;151(5):571-9.
13 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 484).
14 The antihyperalgesic activity of a selective P2X7 receptor antagonist, A-839977, is lost in IL-1alphabeta knockout mice. Behav Brain Res. 2009 Dec 1;204(1):77-81.
15 Mechanism of action of species-selective P2X(7) receptor antagonists. Br J Pharmacol. 2009 Apr;156(8):1312-25.
16 Chelerythrine and other benzophenanthridine alkaloids block the human P2X7 receptor. Br J Pharmacol. 2004 Jul;142(6):1015-9.
17 Decavanadate, a P2X receptor antagonist, and its use to study ligand interactions with P2X7 receptors. Eur J Pharmacol. 2006 Mar 18;534(1-3):19-29.
18 Structure-activity relationship studies of spinorphin as a potent and selective human P2X(3) receptor antagonist. J Med Chem. 2007 Sep 6;50(18):4543-7.
19 Synthesis and structure-activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6053-8.