Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB3VPTO)

• DOT Name: Galanin peptides (GAL)
• Gene Name: GAL
• Related Disease: Familial temporal lobe epilepsy 8
• UniProt ID: GALA_HUMAN
• PDB ID: 7S3O; 7S3Q; 7S3R; 7WQ3; 7WQ4; 7XBD; 7XJJ; 7XJK; 8DHZ; 8DJ4
• Pfam ID: PF01296 ; PF06540
• Sequence:
  MARGSALLLASLLLAAALSASAGLWSPAKEKRGWTLNSAGYLLGPHAVGNHRSFSDKNGL
  TSKRELRPEDDMKPGSFDRSIPENNIMRTIIEFLSFLHLKEAGALDRLLDLPAAASSEDI
  ERS
• Function: Endocrine hormone of the central and peripheral nervous systems that binds and activates the G protein-coupled receptors GALR1, GALR2, and GALR3. This small neuropeptide may regulate diverse physiologic functions including contraction of smooth muscle of the gastrointestinal and genitourinary tract, growth hormone and insulin release and adrenal secretion.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial temporal lobe epilepsy 8	DISQ75RM	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topiramate	DM82Z30	Approved	Galanin peptides (GAL) increases the Weight decreased ADR of Topiramate.	[27]

2 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 Galanin peptides (GAL).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Galanin peptides (GAL).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Galanin peptides (GAL).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Galanin peptides (GAL).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Galanin peptides (GAL).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Galanin peptides (GAL).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Galanin peptides (GAL).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Galanin peptides (GAL).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Galanin peptides (GAL).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Galanin peptides (GAL).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Galanin peptides (GAL).	[10]
Marinol	DM70IK5	Approved	Marinol increases the expression of Galanin peptides (GAL).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Galanin peptides (GAL).	[7]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Galanin peptides (GAL).	[12]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Galanin peptides (GAL).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Galanin peptides (GAL).	[14]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Galanin peptides (GAL).	[15]
Sulindac	DM2QHZU	Approved	Sulindac affects the expression of Galanin peptides (GAL).	[16]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of Galanin peptides (GAL).	[17]
Meclizine	DMS7T13	Approved	Meclizine affects the expression of Galanin peptides (GAL).	[16]
Methazolamide	DM7J2TA	Approved	Methazolamide affects the expression of Galanin peptides (GAL).	[16]
Megestrol	DMDH9KX	Approved	Megestrol affects the expression of Galanin peptides (GAL).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Galanin peptides (GAL).	[18]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Galanin peptides (GAL).	[19]
Verapamil	DMA7PEW	Phase 2/3 Trial	Verapamil affects the expression of Galanin peptides (GAL).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Galanin peptides (GAL).	[21]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Galanin peptides (GAL).	[22]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Galanin peptides (GAL).	[23]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the activity of Galanin peptides (GAL).	[24]
Manganese	DMKT129	Investigative	Manganese increases the expression of Galanin peptides (GAL).	[25]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the activity of Galanin peptides (GAL).	[26]

References

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• [6] Analysis of estrogen agonism and antagonism of tamoxifen, raloxifene, and ICI182780 in endometrial cancer cells: a putative role for the epidermal growth factor receptor ligand amphiregulin. J Soc Gynecol Investig. 2005 Oct;12(7):e55-67.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
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• [12] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [13] NFATc4 mediates ethanol-triggered hepatocyte senescence. Toxicol Lett. 2021 Oct 10;350:10-21. doi: 10.1016/j.toxlet.2021.06.018. Epub 2021 Jun 27.
• [14] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [15] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [16] Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays. Physiol Genomics. 2002 Oct 29;11(2):45-52. doi: 10.1152/physiolgenomics.00064.2002.
• [17] Methamphetamine alters the normal progression by inducing cell cycle arrest in astrocytes. PLoS One. 2014 Oct 7;9(10):e109603.
• [18] 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.
• [19] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [20] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [21] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [22] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [23] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [24] Ochratoxin A induced premature senescence in human renal proximal tubular cells. Toxicology. 2017 May 1;382:75-83. doi: 10.1016/j.tox.2017.03.009. Epub 2017 Mar 9.
• [25] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [26] Low-dose tributyltin triggers human chondrocyte senescence and mouse articular cartilage aging. Arch Toxicol. 2023 Feb;97(2):547-559. doi: 10.1007/s00204-022-03407-x. Epub 2022 Nov 1.
• [27] 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.