Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL4VZ9I)

• DOT Name: P2X purinoceptor 1 (P2RX1)
• Synonyms: P2X1; ATP receptor; Purinergic receptor
• Gene Name: P2RX1
• UniProt ID: P2RX1_HUMAN
• Pfam ID: PF00864
• Sequence:
  MARRFQEELAAFLFEYDTPRMVLVRNKKVGVIFRLIQLVVLVYVIGWVFLYEKGYQTSSG
  LISSVSVKLKGLAVTQLPGLGPQVWDVADYVFPAQGDNSFVVMTNFIVTPKQTQGYCAEH
  PEGGICKEDSGCTPGKAKRKAQGIRTGKCVAFNDTVKTCEIFGWCPVEVDDDIPRPALLR
  EAENFTLFIKNSISFPRFKVNRRNLVEEVNAAHMKTCLFHKTLHPLCPVFQLGYVVQESG
  QNFSTLAEKGGVVGITIDWHCDLDWHVRHCRPIYEFHGLYEEKNLSPGFNFRFARHFVEN
  GTNYRHLFKVFGIRFDILVDGKAGKFDIIPTMTTIGSGIGIFGVATVLCDLLLLHILPKR
  HYYKQKKFKYAEDMGPGAAERDLAATSSTLGLQENMRTS
• Function: Ligand-gated ion channel with relatively high calcium permeability. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle. Seems to be linked to apoptosis, by increasing the intracellular concentration of calcium in the presence of ATP, leading to programmed cell death.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Platelet activation (hsa04611)
• Reactome Pathway:
  Platelet homeostasis (R-HSA-418346)
  Neutrophil degranulation (R-HSA-6798695)
  Elevation of cytosolic Ca2+ levels (R-HSA-139853)

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of P2X purinoceptor 1 (P2RX1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of P2X purinoceptor 1 (P2RX1).	[7]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of P2X purinoceptor 1 (P2RX1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of P2X purinoceptor 1 (P2RX1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of P2X purinoceptor 1 (P2RX1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of P2X purinoceptor 1 (P2RX1).	[5]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 decreases the activity of P2X purinoceptor 1 (P2RX1).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of P2X purinoceptor 1 (P2RX1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of P2X purinoceptor 1 (P2RX1).	[9]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Identification of human P2X1 receptor-interacting proteins reveals a role of the cytoskeleton in receptor regulation. J Biol Chem. 2011 Sep 2;286(35):30591-30599. doi: 10.1074/jbc.M111.253153. Epub 2011 Jul 7.
• [7] 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.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.