Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFDR1WJ)

• DOT Name: Probable G-protein coupled receptor 146 (GPR146)
• Synonyms: G-protein coupled receptor PGR8
• Gene Name: GPR146
• Related Disease:
  Herpes simplex infection
  Type-1/2 diabetes
• UniProt ID: GP146_HUMAN
• Pfam ID: PF00001
• Sequence:
  MWSCSWFNGTGLVEELPACQDLQLGLSLLSLLGLVVGVPVGLCYNALLVLANLHSKASMT
  MPDVYFVNMAVAGLVLSALAPVHLLGPPSSRWALWSVGGEVHVALQIPFNVSSLVAMYST
  ALLSLDHYIERALPRTYMASVYNTRHVCGFVWGGALLTSFSSLLFYICSHVSTRALECAK
  MQNAEAADATLVFIGYVVPALATLYALVLLSRVRREDTPLDRDTGRLEPSAHRLLVATVC
  TQFGLWTPHYLILLGHTVIISRGKPVDAHYLGLLHFVKDFSKLLAFSSSFVTPLLYRYMN
  QSFPSKLQRLMKKLPCGDRHCSPDHMGVQQVLA
• Function: Orphan receptor.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Herpes simplex infection	DISL1SAV	Strong	Altered Expression	[1]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[2]

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 Probable G-protein coupled receptor 146 (GPR146).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Probable G-protein coupled receptor 146 (GPR146).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Probable G-protein coupled receptor 146 (GPR146).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Probable G-protein coupled receptor 146 (GPR146).	[6]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Probable G-protein coupled receptor 146 (GPR146).	[7]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Probable G-protein coupled receptor 146 (GPR146).	[8]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Probable G-protein coupled receptor 146 (GPR146).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Probable G-protein coupled receptor 146 (GPR146).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Probable G-protein coupled receptor 146 (GPR146).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Probable G-protein coupled receptor 146 (GPR146).	[11]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Probable G-protein coupled receptor 146 (GPR146).	[12]

References

• [1] Elimination of GPR146-mediated antiviral function through IRF3/HES1-signalling pathway.Immunology. 2017 Sep;152(1):102-114. doi: 10.1111/imm.12752. Epub 2017 Jun 1.
• [2] Targeting orphan G protein-coupled receptors for the treatment of diabetes and its complications: C-peptide and GPR146.J Intern Med. 2017 Jan;281(1):25-40. doi: 10.1111/joim.12528. Epub 2016 Jun 16.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] 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.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] 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.
• [8] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [9] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [10] 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.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.