Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKRSLV2)

• DOT Name: P2X purinoceptor 3 (P2RX3)
• Synonyms: P2X3; ATP receptor; Purinergic receptor
• Gene Name: P2RX3
• UniProt ID: P2RX3_HUMAN
• PDB ID: 5SVJ; 5SVK; 5SVL; 5SVM; 5SVP; 5SVQ; 5SVR; 5SVS; 5SVT; 5YVE; 6AH4; 6AH5
• Pfam ID: PF00864
• Sequence:
  MNCISDFFTYETTKSVVVKSWTIGIINRVVQLLIISYFVGWVFLHEKAYQVRDTAIESSV
  VTKVKGSGLYANRVMDVSDYVTPPQGTSVFVIITKMIVTENQMQGFCPESEEKYRCVSDS
  QCGPERLPGGGILTGRCVNYSSVLRTCEIQGWCPTEVDTVETPIMMEAENFTIFIKNSIR
  FPLFNFEKGNLLPNLTARDMKTCRFHPDKDPFCPILRVGDVVKFAGQDFAKLARTGGVLG
  IKIGWVCDLDKAWDQCIPKYSFTRLDSVSEKSSVSPGYNFRFAKYYKMENGSEYRTLLKA
  FGIRFDVLVYGNAGKFNIIPTIISSVAAFTSVGVGTVLCDIILLNFLKGADQYKAKKFEE
  VNETTLKIAALTNPVYPSDQTTAEKQSTDSGAFSIGH
• Function: Receptor for ATP that acts as a ligand-gated cation channel. Plays a role in sensory perception. Required for normal perception of pain. Required for normal taste perception.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Taste transduction (hsa04742)
• Reactome Pathway:
  Platelet homeostasis (R-HSA-418346)
  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 3 (P2RX3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of P2X purinoceptor 3 (P2RX3).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of P2X purinoceptor 3 (P2RX3).	[3]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of P2X purinoceptor 3 (P2RX3).	[4]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of P2X purinoceptor 3 (P2RX3).	[5]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of P2X purinoceptor 3 (P2RX3).	[6]

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] 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.
• [3] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [4] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [5] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [6] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.