Target Information
| Target General Information | Top | |||||
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| Target ID |
T63414
(Former ID: TTDC00218)
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| Target Name |
P2X purinoceptor 7 (P2RX7)
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| Synonyms |
Purinergic receptor 7; P2Z receptor; P2X7; Adenosine P2X7 receptor; ATP receptor
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| Gene Name |
P2RX7
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Joint pain [ICD-11: ME82] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
ATP-gated P2X receptor cation channel
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| UniProt ID | ||||||
| Sequence |
MPACCSCSDVFQYETNKVTRIQSMNYGTIKWFFHVIIFSYVCFALVSDKLYQRKEPVISS
VHTKVKGIAEVKEEIVENGVKKLVHSVFDTADYTFPLQGNSFFVMTNFLKTEGQEQRLCP EYPTRRTLCSSDRGCKKGWMDPQSKGIQTGRCVVYEGNQKTCEVSAWCPIEAVEEAPRPA LLNSAENFTVLIKNNIDFPGHNYTTRNILPGLNITCTFHKTQNPQCPIFRLGDIFRETGD NFSDVAIQGGIMGIEIYWDCNLDRWFHHCRPKYSFRRLDDKTTNVSLYPGYNFRYAKYYK ENNVEKRTLIKVFGIRFDILVFGTGGKFDIIQLVVYIGSTLSYFGLAAVFIDFLIDTYSS NCCRSHIYPWCKCCQPCVVNEYYYRKKCESIVEPKPTLKYVSFVDESHIRMVNQQLLGRS LQDVKGQEVPRPAMDFTDLSRLPLALHDTPPIPGQPEEIQLLRKEATPRSRDSPVWCQCG SCLPSQLPESHRCLEELCCRKKPGACITTSELFRKLVLSRHVLQFLLLYQEPLLALDVDS TNSRLRHCAYRCYATWRFGSQDMADFAILPSCCRWRIRKEFPKSEGQYSGFKSPY Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T54B00 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 9 Clinical Trial Drugs | + | ||||
| 1 | CE-224535 | Drug Info | Phase 2/3 | Arthralgia | [2] | |
| 2 | AZD9056 | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [3], [4] | |
| 3 | BIL010t | Drug Info | Phase 1/2 | Solid tumour/cancer | [5] | |
| 4 | EVT 401 | Drug Info | Phase 1 | Rheumatoid arthritis | [6] | |
| 5 | GSK1482160 | Drug Info | Phase 1 | Pain | [7] | |
| 6 | JNJ-54175446 | Drug Info | Phase 1 | Major depressive disorder | [8] | |
| 7 | JNJ-55308942 | Drug Info | Phase 1 | Anhedonia | [5] | |
| 8 | SGM-1019 | Drug Info | Phase 1 | Inflammatory bowel disease | [9] | |
| 9 | JNJ-479655 | Drug Info | Clinical trial | Alzheimer disease | [10] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Antagonist | [+] 47 Antagonist drugs | + | ||||
| 1 | CE-224535 | Drug Info | [1] | |||
| 2 | AZD9056 | Drug Info | [11] | |||
| 3 | EVT 401 | Drug Info | [12] | |||
| 4 | GSK1482160 | Drug Info | [13] | |||
| 5 | JNJ-54175446 | Drug Info | [8] | |||
| 6 | JNJ-479655 | Drug Info | [14] | |||
| 7 | Aminobenzoxazole analog 1 | Drug Info | [15] | |||
| 8 | Benzamide derivative 12 | Drug Info | [15] | |||
| 9 | Benzamide derivative 13 | Drug Info | [15] | |||
| 10 | Bicyclic heteroaryl amide derivative 1 | Drug Info | [15] | |||
| 11 | Bicyclic heteroaryl amide derivative 2 | Drug Info | [15] | |||
| 12 | Bicyclic heteroaryl amide derivative 3 | Drug Info | [15] | |||
| 13 | Chlorobenzamide derivative 1 | Drug Info | [15] | |||
| 14 | Chlorobenzamide derivative 2 | Drug Info | [15] | |||
| 15 | Dihydroisoquinoline carboxamide analog 1 | Drug Info | [15] | |||
| 16 | Fluorophenyl-substituted heterocyclic amide analog 1 | Drug Info | [15] | |||
| 17 | Fused triazoloamino-phenyl analog 1 | Drug Info | [15] | |||
| 18 | Heterocyclic-fused piperazine derivative 1 | Drug Info | [15] | |||
| 19 | Imidazolidine derivative 1 | Drug Info | [15] | |||
| 20 | Indole carboxamide derivative 1 | Drug Info | [15] | |||
| 21 | Isoindole 1,3-dione analog 1 | Drug Info | [15] | |||
| 22 | Isothiazolidine derivative 1 | Drug Info | [15] | |||
| 23 | Piperazine derivative 6 | Drug Info | [15] | |||
| 24 | Piperidinone derivative 1 | Drug Info | [15] | |||
| 25 | PMID27724045-Compound-14 | Drug Info | [15] | |||
| 26 | PMID27724045-Compound-15 | Drug Info | [15] | |||
| 27 | PMID27724045-Compound-17 | Drug Info | [15] | |||
| 28 | PMID27724045-Compound-19 | Drug Info | [15] | |||
| 29 | PMID27724045-Compound-29 | Drug Info | [15] | |||
| 30 | PMID27724045-Compound-33 | Drug Info | [15] | |||
| 31 | Pyridazinone derivative 1 | Drug Info | [15] | |||
| 32 | Quinoline derivative 10 | Drug Info | [15] | |||
| 33 | Quinoline derivative 11 | Drug Info | [15] | |||
| 34 | Quinoline derivative 12 | Drug Info | [15] | |||
| 35 | Quinoline derivative 13 | Drug Info | [15] | |||
| 36 | Tetrazole derivative 1 | Drug Info | [15] | |||
| 37 | Thiazole derivative 5 | Drug Info | [15] | |||
| 38 | Thiazole-fused cycloalkyl carboxamide derivative 1 | Drug Info | [15] | |||
| 39 | Triazole derivative 2 | Drug Info | [15] | |||
| 40 | Triazolo-pyrazinone derivative 1 | Drug Info | [15] | |||
| 41 | A438079 | Drug Info | [17] | |||
| 42 | A804598 | Drug Info | [18] | |||
| 43 | A839977 | Drug Info | [19] | |||
| 44 | AFC-5128 | Drug Info | [18] | |||
| 45 | AZ-11657312 | Drug Info | [18] | |||
| 46 | AZ11657312 (salt free) | Drug Info | [18] | |||
| 47 | decavanadate | Drug Info | [22] | |||
| Inhibitor | [+] 6 Inhibitor drugs | + | ||||
| 1 | JNJ-55308942 | Drug Info | [5] | |||
| 2 | A-740003 | Drug Info | [16] | |||
| 3 | ISOPPADS | Drug Info | [23] | |||
| 4 | KN-62 | Drug Info | [24] | |||
| 5 | STYLISSADINE A | Drug Info | [16] | |||
| 6 | STYLISSADINE B | Drug Info | [16] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | SGM-1019 | Drug Info | [9] | |||
| Modulator (allosteric modulator) | [+] 2 Modulator (allosteric modulator) drugs | + | ||||
| 1 | AZ11645373 | Drug Info | [20] | |||
| 2 | chelerythrine | Drug Info | [21] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Calcium signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | The NLRP3 inflammasome | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | ClinicalTrials.gov (NCT00628095) Study of CE-224,535 A Twice Daily Pill To Control Rheumatoid Arthritis In Patients Who Have Not Totally Improved With Methotrexate. U.S. National Institutes of Health. | |||||
| REF 3 | 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. (Ligand id: 7826). | |||||
| REF 4 | ClinicalTrials.gov (NCT00520572) A 6-month Randomised, Double-blind, Open Arm Comparator, Phase IIb, With AZD9056, in Patients With Rheumatoid Arthritis (RA). U.S. National Institutes of Health. | |||||
| REF 5 | Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357. | |||||
| REF 6 | Clinical pipeline report, company report or official report of Evotec. | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029786) | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 10 | The role of the innate immune system in psychiatric disorders. Mol Cell Neurosci. 2013 Mar;53:52-62. | |||||
| REF 11 | Clinical pipeline report, company report or official report of AstraZeneca (2009). | |||||
| REF 12 | Molecular and functional properties of P2X receptors ecent progress and persisting challenges. Purinergic Signal. 2012 September; 8(3): 375-417. | |||||
| REF 13 | Clinical pipeline report, company report or official report of GlaxoSmithKline (2009). | |||||
| REF 14 | Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br J Pharmacol. 2013 Oct;170(3):624-40. | |||||
| REF 15 | P2X7 receptor antagonists: a patent review (2010-2015).Expert Opin Ther Pat. 2017 Mar;27(3):257-267. | |||||
| REF 16 | Purinergic P2X(7) receptor antagonists: Chemistry and fundamentals of biological screening. Bioorg Med Chem. 2009 Jul 15;17(14):4861-5. | |||||
| REF 17 | 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. | |||||
| REF 18 | 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). | |||||
| REF 19 | 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. | |||||
| REF 20 | Mechanism of action of species-selective P2X(7) receptor antagonists. Br J Pharmacol. 2009 Apr;156(8):1312-25. | |||||
| REF 21 | Chelerythrine and other benzophenanthridine alkaloids block the human P2X7 receptor. Br J Pharmacol. 2004 Jul;142(6):1015-9. | |||||
| REF 22 | 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. | |||||
| REF 23 | 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. | |||||
| REF 24 | Synthesis and structure-activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6053-8. | |||||
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