Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5V52LN)

DOT Name Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A)
Synonyms Fibroblast growth factor-inducible immediate-early response protein 14; FGF-inducible 14; Tweak-receptor; TweakR; CD antigen CD266
Gene Name TNFRSF12A
UniProt ID
TNR12_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2EQP; 2KMZ; 2RPJ
Pfam ID
PF12191
Sequence
MARGSLRRLLRLLVLGLWLALLRSVAGEQAPGTAPCSRGSSWSADLDKCMDCASCRARPH
SDFCLGCAAAPPAPFRLLWPILGGALSLTFVLGLLSGFLVWRRCRRREKFTTPIEETGGE
GCPAVALIQ
Function Receptor for TNFSF12/TWEAK. Weak inducer of apoptosis in some cell types. Promotes angiogenesis and the proliferation of endothelial cells. May modulate cellular adhesion to matrix proteins.
Tissue Specificity Highly expressed in heart, placenta and kidney. Intermediate expression in lung, skeletal muscle and pancreas.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Reactome Pathway
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway (R-HSA-5676594 )
TNFR2 non-canonical NF-kB pathway (R-HSA-5668541 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
41 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [1]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [2]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [3]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [6]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [7]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [8]
Quercetin DM3NC4M Approved Quercetin increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [9]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [11]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [12]
Testosterone DM7HUNW Approved Testosterone increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [12]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [13]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [14]
Marinol DM70IK5 Approved Marinol decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [15]
Selenium DM25CGV Approved Selenium increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [16]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [17]
Menadione DMSJDTY Approved Menadione affects the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [18]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [19]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [20]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [21]
Hydroquinone DM6AVR4 Approved Hydroquinone increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [22]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [23]
Ethanol DMDRQZU Approved Ethanol decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [24]
Etoposide DMNH3PG Approved Etoposide increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [7]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [19]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [25]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [9]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [26]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [27]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [28]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [29]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [30]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [31]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [32]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [33]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [34]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [35]
Arachidonic acid DMUOQZD Investigative Arachidonic acid increases the expression of Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A). [36]
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⏷ Show the Full List of 41 Drug(s)

References

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10 Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
11 Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Dec;334:113466. doi: 10.1016/j.expneurol.2020.113466. Epub 2020 Sep 17.
12 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
13 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.
14 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
15 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
16 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.
17 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.
18 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.
19 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.
20 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
21 Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
22 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
23 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
24 Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
25 Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
26 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
27 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
28 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.
29 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
30 Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
31 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
32 Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
33 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
34 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
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36 Arachidonic acid-induced gene expression in colon cancer cells. Carcinogenesis. 2006 Oct;27(10):1950-60.