Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT91UMQC)

• DOT Name: Prostaglandin reductase 3 (PTGR3)
• Synonyms: PRG-3; EC 1.3.1.48; Zinc-binding alcohol dehydrogenase domain-containing protein 2
• Gene Name: PTGR3
• UniProt ID: PTGR3_HUMAN
• PDB ID: 2C0C; 2WEK; 2X1H; 2X7H; 7ZEJ
• EC Number: 1.3.1.48
• Pfam ID: PF08240 ; PF00107
• Sequence:
  MLRLVPTGARAIVDMSYARHFLDFQGSAIPQAMQKLVVTRLSPNFREAVTLSRDCPVPLP
  GDGDLLVRNRFVGVNASDINYSAGRYDPSVKPPFDIGFEGIGEVVALGLSASARYTVGQA
  VAYMAPGSFAEYTVVPASIATPVPSVKPEYLTLLVSGTTAYISLKELGGLSEGKKVLVTA
  AAGGTGQFAMQLSKKAKCHVIGTCSSDEKSAFLKSLGCDRPINYKTEPVGTVLKQEYPEG
  VDVVYESVGGAMFDLAVDALATKGRLIVIGFISGYQTPTGLSPVKAGTLPAKLLKKSASV
  QGFFLNHYLSKYQAAMSHLLEMCVSGDLVCEVDLGDLSPEGRFTGLESIFRAVNYMYMGK
  NTGKIVVELPHSVNSKL
• Function: Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest efficiency towards 15-keto-PGE2-alpha. Overexpression represses transcriptional activity of PPARG and inhibits adipocyte differentiation.
• KEGG Pathway: Arachidonic acid metabolism (hsa00590)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Prostaglandin reductase 3 (PTGR3).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Prostaglandin reductase 3 (PTGR3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Prostaglandin reductase 3 (PTGR3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prostaglandin reductase 3 (PTGR3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Prostaglandin reductase 3 (PTGR3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Prostaglandin reductase 3 (PTGR3).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prostaglandin reductase 3 (PTGR3).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Prostaglandin reductase 3 (PTGR3).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Prostaglandin reductase 3 (PTGR3).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Prostaglandin reductase 3 (PTGR3).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Prostaglandin reductase 3 (PTGR3).	[1]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Prostaglandin reductase 3 (PTGR3).	[1]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Prostaglandin reductase 3 (PTGR3).	[10]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Prostaglandin reductase 3 (PTGR3).	[12]

1 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 reductase 3 (PTGR3).	[8]

References

• [1] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [7] 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.
• [8] 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.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.