Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMDRXCP)

• Drug Name: AZ11645373 Drug Info
• Synonyms: AZ 11645373; AZ-11645373

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9804433
  CAS Number: CAS 227088-94-0
  TTD Drug ID: DMDRXCP

Molecule-Related Drug Atlas

Drug(s) Targeting P2X purinoceptor 7 (P2RX7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CE-224535	DMFCLT6	Arthralgia	ME82	Phase 2/3	[4]
AZD9056	DMJGYPK	Chronic obstructive pulmonary disease	CA22	Phase 2	[5]
LY3857210	DMZO2V2	Pain	MG30-MG3Z	Phase 2	[6]
BIL010t	DMV1EA9	Alzheimer disease	8A20	Phase 1/2	[7]
EVT 401	DMOG8IE	Rheumatoid arthritis	FA20	Phase 1	[8]
SGM-1019	DMDAHEL	Inflammatory bowel disease	DD72	Phase 1	[9]
GSK1482160	DMWDQOV	Pain	MG30-MG3Z	Phase 1	[10]
JNJ-55308942	DM0QZJX	Anhedonia	MB24.2	Phase 1	[7]
JNJ-54175446	DMQ5ZVK	Major depressive disorder	6A70.3	Phase 1	[11]
JNJ-479655	DMDU6GN	Alzheimer disease	8A20	Clinical trial	[12]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[13]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[14]
Adenosine triphosphate	DM79F6G	Malnutrition	5B50-5B71	Approved	[15]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[18]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[19]
BzATP	DM37GYA	Discovery agent	N.A.	Investigative	[20]
Milchsaure	DM462BT	Pruritus	EC90	Investigative	[21]
Ethidium	DMMEQUR	Discovery agent	N.A.	Investigative	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
P2X purinoceptor 7 (P2RX7)	TT473XN	P2RX7_HUMAN	Modulator (allosteric modulator)	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
P2X purinoceptor 7 (P2RX7)	OTNJ9XPL	P2RX7_HUMAN	Protein Interaction/Cellular Processes	[3]

References

• [1] 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: 4142).
• [2] Mechanism of action of species-selective P2X(7) receptor antagonists. Br J Pharmacol. 2009 Apr;156(8):1312-25.
• [3] Mapping the Site of Action of Human P2X7 Receptor Antagonists AZ11645373, Brilliant Blue G, KN-62, Calmidazolium, and ZINC58368839 to the Intersubunit Allosteric Pocket. Mol Pharmacol. 2019 Sep;96(3):355-363. doi: 10.1124/mol.119.116715. Epub 2019 Jul 1.
• [4] 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.
• [5] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
• [7] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [8] Molecular and functional properties of P2X receptors ecent progress and persisting challenges. Purinergic Signal. 2012 September; 8(3): 375-417.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br J Pharmacol. 2013 Oct;170(3):624-40.
• [13] Epidermal growth factor facilitates epinephrine inhibition of P2X7-receptor-mediated pore formation and apoptosis: a novel signaling network. Endocrinology. 2005 Jan;146(1):164-74. doi: 10.1210/en.2004-1026. Epub 2004 Sep 30.
• [14] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Pharmacological characterization of pannexin-1 currents expressed in mammalian cells. J Pharmacol Exp Ther. 2009 Feb;328(2):409-18. doi: 10.1124/jpet.108.146365. Epub 2008 Nov 20.
• [16] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [17] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [18] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [19] Bisphenol A, Bisphenol F, and Bisphenol S: The Bad and the Ugly. Where Is the Good?. Life (Basel). 2021 Apr 3;11(4):314. doi: 10.3390/life11040314.
• [20] -Nicotinamide Adenine Dinucleotide (-NAD) Inhibits ATP-Dependent IL-1 Release from Human Monocytic Cells. Int J Mol Sci. 2018 Apr 10;19(4):1126. doi: 10.3390/ijms19041126.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] A Thr357 to Ser polymorphism in homozygous and compound heterozygous subjects causes absent or reduced P2X7 function and impairs ATP-induced mycobacterial killing by macrophages. J Biol Chem. 2006 Jan 27;281(4):2079-86. doi: 10.1074/jbc.M507816200. Epub 2005 Nov 1.