Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB7YQFU)

• DOT Name: Prostaglandin E synthase (PTGES)
• Synonyms: EC 5.3.99.3; Glutathione peroxidase PTGES; EC 1.11.1.-; Glutathione transferase PTGES; EC 2.5.1.18; Microsomal glutathione S-transferase 1-like 1; MGST1-L1; Microsomal prostaglandin E synthase 1; MPGES-1; p53-induced gene 12 protein
• Gene Name: PTGES
• UniProt ID: PTGES_HUMAN
• PDB ID: 3DWW; 4AL0; 4AL1; 4BPM; 4WAB; 4YK5; 4YL0; 4YL1; 4YL3; 5BQG; 5BQH; 5BQI; 5K0I; 5T36; 5T37; 5TL9; 6VL4; 8PYV
• EC Number: 1.11.1.-; 2.5.1.18; 5.3.99.3
• Pfam ID: PF01124
• Sequence:
  MPAHSLVMSSPALPAFLLCSTLLVIKMYVVAIITGQVRLRKKAFANPEDALRHGGPQYCR
  SDPDVERCLRAHRNDMETIYPFLFLGFVYSFLGPNPFVAWMHFLVFLVGRVAHTVAYLGK
  LRAPIRSVTYTLAQLPCASMALQILWEAARHL
• Function: Terminal enzyme of the cyclooxygenase (COX)-2-mediated prostaglandin E2 (PGE2) biosynthetic pathway. Catalyzes the glutathione-dependent oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) in response to inflammatory stimuli. Plays a key role in inflammation response, fever and pain. Catalyzes also the oxidoreduction of endocannabinoids into prostaglandin glycerol esters and PGG2 into 15-hydroperoxy-PGE2. In addition, displays low glutathione transferase and glutathione-dependent peroxidase activities, toward 1-chloro-2,4-dinitrobenzene and 5-hydroperoxyicosatetraenoic acid (5-HPETE), respectively.
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123)
• BioCyc Pathway: MetaCyc:HS07518-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dinoprostone	DMTYOPD	Approved	Prostaglandin E synthase (PTGES) increases the abundance of Dinoprostone.	[25]

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 Prostaglandin E synthase (PTGES).	[1]

30 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 Prostaglandin E synthase (PTGES).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prostaglandin E synthase (PTGES).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Prostaglandin E synthase (PTGES).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Prostaglandin E synthase (PTGES).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Prostaglandin E synthase (PTGES).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Prostaglandin E synthase (PTGES).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Prostaglandin E synthase (PTGES).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Prostaglandin E synthase (PTGES).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Prostaglandin E synthase (PTGES).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Prostaglandin E synthase (PTGES).	[9]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Prostaglandin E synthase (PTGES).	[11]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Prostaglandin E synthase (PTGES).	[12]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Prostaglandin E synthase (PTGES).	[13]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Prostaglandin E synthase (PTGES).	[14]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Prostaglandin E synthase (PTGES).	[15]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Prostaglandin E synthase (PTGES).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Prostaglandin E synthase (PTGES).	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Prostaglandin E synthase (PTGES).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Prostaglandin E synthase (PTGES).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Prostaglandin E synthase (PTGES).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the expression of Prostaglandin E synthase (PTGES).	[18]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL increases the expression of Prostaglandin E synthase (PTGES).	[9]
MK-886	DMT0O7H	Discontinued in Phase 2	MK-886 decreases the activity of Prostaglandin E synthase (PTGES).	[19]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the activity of Prostaglandin E synthase (PTGES).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Prostaglandin E synthase (PTGES).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Prostaglandin E synthase (PTGES).	[22]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol increases the expression of Prostaglandin E synthase (PTGES).	[23]
gingerol	DMNXYSM	Investigative	gingerol increases the expression of Prostaglandin E synthase (PTGES).	[24]
24(S)-hydroxycholesterol	DMGMWA6	Investigative	24(S)-hydroxycholesterol increases the expression of Prostaglandin E synthase (PTGES).	[23]
7alpha-hydroxycholesterol	DMH6LD0	Investigative	7alpha-hydroxycholesterol increases the expression of Prostaglandin E synthase (PTGES).	[23]

References

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• [11] Aspirin inhibits MMP-9 mRNA expression and release via the PPARalpha/gamma and COX-2/mPGES-1-mediated pathways in macrophages derived from THP-1 cells. Biomed Pharmacother. 2010 Feb;64(2):118-23. doi: 10.1016/j.biopha.2009.04.033. Epub 2009 Oct 17.
• [12] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
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• [14] Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2716-23.
• [15] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
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• [19] Arzanol, a prenylated heterodimeric phloroglucinyl pyrone, inhibits eicosanoid biosynthesis and exhibits anti-inflammatory efficacy in vivo. Biochem Pharmacol. 2011 Jan 15;81(2):259-68.
• [20] Interference of alpha-alkyl-substituted pirinixic acid derivatives with neutrophil functions and signalling pathways. Eur J Pharmacol. 2009 Oct 1;619(1-3):1-7.
• [21] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Loading into nanoparticles improves quercetin's efficacy in preventing neuroinflammation induced by oxysterols. PLoS One. 2014 May 6;9(5):e96795.
• [24] Revealing the effect of 6-gingerol, 6-shogaol and curcumin on mPGES-1, GSK-3 and -catenin pathway in A549 cell line. Chem Biol Interact. 2016 Oct 25;258:257-65. doi: 10.1016/j.cbi.2016.09.012. Epub 2016 Sep 16.
• [25] Increase in PGE2 biosynthesis induces a Bax dependent apoptosis correlated to patients' survival in glioblastoma multiforme. Oncogene. 2007 Jul 26;26(34):4999-5009. doi: 10.1038/sj.onc.1210303. Epub 2007 Mar 19.