Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMS4J0P)

• DOT Name: Prostaglandin E synthase 2 (PTGES2)
• Synonyms: EC 5.3.99.3; Membrane-associated prostaglandin E synthase-2; mPGE synthase-2; Microsomal prostaglandin E synthase 2; mPGES-2; Prostaglandin-H(2) E-isomerase
• Gene Name: PTGES2
• UniProt ID: PGES2_HUMAN
• EC Number: 5.3.99.3
• Pfam ID: PF13410 ; PF13417
• Sequence:
  MDPAARVVRALWPGGCALAWRLGGRPQPLLPTQSRAGFAGAAGGPSPVAAARKGSPRLLG
  AAALALGGALGLYHTARWHLRAQDLHAERSAAQLSLSSRLQLTLYQYKTCPFCSKVRAFL
  DFHALPYQVVEVNPVRRAEIKFSSYRKVPILVAQEGESSQQLNDSSVIISALKTYLVSGQ
  PLEEIITYYPAMKAVNEQGKEVTEFGNKYWLMLNEKEAQQVYGGKEARTEEMKWRQWADD
  WLVHLISPNVYRTPTEALASFDYIVREGKFGAVEGAVAKYMGAAAMYLISKRLKSRHRLQ
  DNVREDLYEAADKWVAAVGKDRPFMGGQKPNLADLAVYGVLRVMEGLDAFDDLMQHTHIQ
  PWYLRVERAITEASPAH
• Function: Isomerase that catalyzes the conversion of PGH2 into the more stable prostaglandin E2 (PGE2) (in vitro). The biological function and the GSH-dependent property of PTGES2 is still under debate. In vivo, PTGES2 could form a complex with GSH and heme and would not participate in PGE2 synthesis but would catalyze the degradation of prostaglandin E2 H2 (PGH2) to 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid (HHT) and malondialdehyde (MDA).
• Tissue Specificity: Widely expressed. Expressed in the heart, including apex, inter-ventricular septum, both atria and ventricles, but not in the aorta. Also expressed in fetal heart. Detected in various regions of the brain: cerebellum; occipital, frontal and parietal lobes. Also expressed in the lymph nodes, skeletal muscle, kidney and trachea, but not in the thymus or lung. Overexpressed in colorectal cancer.
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123)
• BioCyc Pathway: MetaCyc:HS07514-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Prostaglandin E synthase 2 (PTGES2).	[1]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prostaglandin E synthase 2 (PTGES2).	[2]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Prostaglandin E synthase 2 (PTGES2).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Prostaglandin E synthase 2 (PTGES2).	[5]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the activity of Prostaglandin E synthase 2 (PTGES2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Prostaglandin E synthase 2 (PTGES2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Prostaglandin E synthase 2 (PTGES2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Prostaglandin E synthase 2 (PTGES2).	[6]

References

• [1] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [2] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] Effects of Wy14643 on hepatic ischemia reperfusion injury in rats. World J Gastroenterol. 2008 Dec 7;14(45):6936-42.
• [8] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.