Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJJQ9WI)

• DOT Name: P2Y purinoceptor 11 (P2RY11)
• Synonyms: P2Y11
• Gene Name: P2RY11
• UniProt ID: P2Y11_HUMAN
• Pfam ID: PF00001
• Sequence:
  MAANVSGAKSCPANFLAAADDKLSGFQGDFLWPILVVEFLVAVASNGLALYRFSIRKQRP
  WHPAVVFSVQLAVSDLLCALTLPPLAAYLYPPKHWRYGEAACRLERFLFTCNLLGSVIFI
  TCISLNRYLGIVHPFFARSHLRPKHAWAVSAAGWVLAALLAMPTLSFSHLKRPQQGAGNC
  SVARPEACIKCLGTADHGLAAYRAYSLVLAGLGCGLPLLLTLAAYGALGRAVLRSPGMTV
  AEKLRVAALVASGVALYASSYVPYHIMRVLNVDARRRWSTRCPSFADIAQATAALELGPY
  VGYQVMRGLMPLAFCVHPLLYMAAVPSLGCCCRHCPGYRDSWNPEDAKSTGQALPLNATA
  APKPSEPQSRELSQ
• Function: Receptor for ATP and ADP coupled to G-proteins that activate both phosphatidylinositol-calcium and adenylyl cyclase second messenger systems. Not activated by UTP or UDP.
• Tissue Specificity: Highest expression in liver and spleen.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  P2Y receptors (R-HSA-417957)
  G alpha (s) signalling events (R-HSA-418555)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

1 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 P2Y purinoceptor 11 (P2RY11).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of P2Y purinoceptor 11 (P2RY11).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of P2Y purinoceptor 11 (P2RY11).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of P2Y purinoceptor 11 (P2RY11).	[4]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of P2Y purinoceptor 11 (P2RY11).	[3]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of P2Y purinoceptor 11 (P2RY11).	[6]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of P2Y purinoceptor 11 (P2RY11).	[7]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Adenosine triphosphate	DM79F6G	Approved	Adenosine triphosphate affects the binding of P2Y purinoceptor 11 (P2RY11).	[5]

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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] P2Y11 impairs cell proliferation by induction of cell cycle arrest and sensitizes endothelial cells to cisplatin-induced cell death. J Cell Biochem. 2011 Sep;112(9):2257-65. doi: 10.1002/jcb.23144.
• [6] 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.
• [7] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.