Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6QGBYE)

• DOT Name: Opioid growth factor receptor-like protein 1 (OGFRL1)
• Gene Name: OGFRL1
• UniProt ID: OGRL1_HUMAN
• Pfam ID: PF04664
• Sequence:
  MGNLLGGVSFREPTTVEDCDSTWQTDSEPEPEEPGPGGGSEGPGQESEQPAQPPEQAGGR
  PGASPAPDEDAEAAGAEQGGDSTEATAKPKRSFYAARDLYKYRHQYPNFKDIRYQNDLSN
  LRFYKNKIPFKPDGVYIEEVLSKWKGDYEKLEHNHTYIQWLFPLREQGLNFYAKELTTYE
  IEEFKKTKEAIRRFLLAYKMMLEFFGIKLTDKTGNVARAVNWQERFQHLNESQHNYLRIT
  RILKSLGELGYESFKSPLVKFILHEALVENTIPNIKQSALEYFVYTIRDRRERRKLLRFA
  QKHYTPSENFIWGPPRKEQSEGSKAQKMSSPLASSHNSQTSMHKKAKDSKNSSSAVHLNS
  KTAEDKKVAPKEPVEETDRPSPEPSNEAAKPRNTEKDSNAENMNSQPEKTVTTPTEKKES
  VSPENNEEGGNDNQDNENPGNTNCHDVVLVQ
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Opioid growth factor receptor-like protein 1 (OGFRL1) affects the response to substance of Fluorouracil.	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Opioid growth factor receptor-like protein 1 (OGFRL1).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Opioid growth factor receptor-like protein 1 (OGFRL1).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[13]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[16]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[20]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[21]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Opioid growth factor receptor-like protein 1 (OGFRL1).	[22]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [9] 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.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 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.
• [17] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [18] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [19] 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.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [22] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [23] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.