Details of Drug Off-Target (DOT)

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

• DOT Name: Prostaglandin E2 receptor EP3 subtype (PTGER3)
• Synonyms: PGE receptor EP3 subtype; PGE2 receptor EP3 subtype; PGE2-R; Prostanoid EP3 receptor
• Gene Name: PTGER3
• UniProt ID: PE2R3_HUMAN
• PDB ID: 6AK3; 6M9T; 7WU9
• Pfam ID: PF00001
• Sequence:
  MKETRGYGGDAPFCTRLNHSYTGMWAPERSAEARGNLTRPPGSGEDCGSVSVAFPITMLL
  TGFVGNALAMLLVSRSYRRRESKRKKSFLLCIGWLALTDLVGQLLTTPVVIVVYLSKQRW
  EHIDPSGRLCTFFGLTMTVFGLSSLFIASAMAVERALAIRAPHWYASHMKTRATRAVLLG
  VWLAVLAFALLPVLGVGQYTVQWPGTWCFISTGRGGNGTSSSHNWGNLFFASAFAFLGLL
  ALTVTFSCNLATIKALVSRCRAKATASQSSAQWGRITTETAIQLMGIMCVLSVCWSPLLI
  MMLKMIFNQTSVEHCKTHTEKQKECNFFLIAVRLASLNQILDPWVYLLLRKILLRKFCQI
  RYHTNNYASSSTSLPCQCSSTLMWSDHLER
• Function: Receptor for prostaglandin E2 (PGE2). The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G(i) proteins, and to an elevation of intracellular calcium. Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality.
• Tissue Specificity: Detected in kidney . Expressed in small intestine, heart, pancreas, gastric fundic mucosa, mammary artery and pulmonary vessels.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Regulation of lipolysis in adipocytes (hsa04923)
  Human cytomegalovirus infection (hsa05163)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Prostanoid ligand receptors (R-HSA-391908)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Prostaglandin E2 receptor EP3 subtype (PTGER3) affects the response to substance of Aspirin.	[12]
Terbinafine	DMI6HUW	Approved	Prostaglandin E2 receptor EP3 subtype (PTGER3) increases the response to substance of Terbinafine.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[3]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[4]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[5]
Rofecoxib	DM3P5DA	Approved	Rofecoxib decreases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[3]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[8]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[3]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Prostaglandin E2 receptor EP3 subtype (PTGER3).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [4] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [5] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [6] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [7] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [8] 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.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Association of PTGER gene family polymorphisms with aspirin intolerant asthma in Korean asthmatics. BMB Rep. 2010 Jun;43(6):445-9. doi: 10.5483/bmbrep.2010.43.6.445.
• [13] Suppressive effects of antimycotics on tumor necrosis factor-alpha-induced CCL27, CCL2, and CCL5 production in human keratinocytes. Biochem Pharmacol. 2006 Aug 14;72(4):463-73. doi: 10.1016/j.bcp.2006.05.001. Epub 2006 Jun 19.