Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTROS6RJ)

• DOT Name: Opioid growth factor receptor (OGFR)
• Synonyms: OGFr; Protein 7-60; Zeta-type opioid receptor
• Gene Name: OGFR
• UniProt ID: OGFR_HUMAN
• Pfam ID: PF04680 ; PF04664
• Sequence:
  MDDPDCDSTWEEDEEDAEDAEDEDCEDGEAAGARDADAGDEDEESEEPRAARPSSFQSRM
  TGSRNWRATRDMCRYRHNYPDLVERDCNGDTPNLSFYRNEIRFLPNGCFIEDILQNWTDN
  YDLLEDNHSYIQWLFPLREPGVNWHAKPLTLREVEVFKSSQEIQERLVRAYELMLGFYGI
  RLEDRGTGTVGRAQNYQKRFQNLNWRSHNNLRITRILKSLGELGLEHFQAPLVRFFLEET
  LVRRELPGVRQSALDYFMFAVRCRHQRRQLVHFAWEHFRPRCKFVWGPQDKLRRFKPSSL
  PHPLEGSRKVEEEGSPGDPDHEASTQGRTCGPEHSKGGGRVDEGPQPRSVEPQDAGPLER
  SQGDEAGGHGEDRPEPLSPKESKKRKLELSRREQPPTEPGPQSASEVEKIALNLEGCALS
  QGSLRTGTQEVGGQDPGEAVQPCRQPLGARVADKVRKRRKVDEGAGDSAAVASGGAQTLA
  LAGSPAPSGHPKAGHSENGVEEDTEGRTGPKEGTPGSPSETPGPSPAGPAGDEPAESPSE
  TPGPRPAGPAGDEPAESPSETPGPRPAGPAGDEPAESPSETPGPSPAGPTRDEPAESPSE
  TPGPRPAGPAGDEPAESPSETPGPRPAGPAGDEPAESPSETPGPSPAGPTRDEPAKAGEA
  AELQDAEVESSAKSGKP
• Function: Receptor for opioid growth factor (OGF), also known as Met-enkephalin. Seems to be involved in growth regulation.
• Tissue Specificity: Highly expressed in the heart and liver, moderately in skeletal muscle and kidney and to a lesser extent in brain and pancreas. Expressed in fetal tissues including liver and kidney.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Opioid growth factor receptor (OGFR) increases the Alcohol poisoning ADR of Ethanol.	[17]
Levodopa	DMN3E57	Approved	Opioid growth factor receptor (OGFR) increases the Parkinson's disease ADR of Levodopa.	[17]
Fentanyl	DM8WAHT	Approved	Opioid growth factor receptor (OGFR) increases the Pain ADR of Fentanyl.	[17]

4 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 Opioid growth factor receptor (OGFR).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Opioid growth factor receptor (OGFR).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Opioid growth factor receptor (OGFR).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Opioid growth factor receptor (OGFR).	[15]

15 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 Opioid growth factor receptor (OGFR).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Opioid growth factor receptor (OGFR).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Opioid growth factor receptor (OGFR).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Opioid growth factor receptor (OGFR).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Opioid growth factor receptor (OGFR).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Opioid growth factor receptor (OGFR).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Opioid growth factor receptor (OGFR).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Opioid growth factor receptor (OGFR).	[10]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Opioid growth factor receptor (OGFR).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Opioid growth factor receptor (OGFR).	[12]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Opioid growth factor receptor (OGFR).	[5]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Opioid growth factor receptor (OGFR).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Opioid growth factor receptor (OGFR).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Opioid growth factor receptor (OGFR).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Opioid growth factor receptor (OGFR).	[16]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [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] 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.
• [6] 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.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [17] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.