Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNGA2BW)

DOT Name Tumor necrosis factor ligand superfamily member 15 (TNFSF15)
Synonyms TNF ligand-related molecule 1; Vascular endothelial cell growth inhibitor
Gene Name TNFSF15
UniProt ID
TNF15_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2O0O; 2QE3; 2RE9; 2RJK; 2RJL; 3K51; 3MI8
Pfam ID
PF00229
Sequence
MAEDLGLSFGETASVEMLPEHGSCRPKARSSSARWALTCCLVLLPFLAGLTTYLLVSQLR
AQGEACVQFQALKGQEFAPSHQQVYAPLRADGDKPRAHLTVVRQTPTQHFKNQFPALHWE
HELGLAFTKNRMNYTNKFLLIPESGDYFIYSQVTFRGMTSECSEIRQAGRPNKPDSITVV
ITKVTDSYPEPTQLLMGTKSVCEVGSNWFQPIYLGAMFSLQEGDKLMVNVSDISLVDYTK
EDKTFFGAFLL
Function Receptor for TNFRSF25 and TNFRSF6B. Mediates activation of NF-kappa-B. Inhibits vascular endothelial growth and angiogenesis (in vitro). Promotes activation of caspases and apoptosis.
Tissue Specificity Specifically expressed in endothelial cells. Detected in monocytes, placenta, lung, liver, kidney, skeletal muscle, pancreas, spleen, prostate, small intestine and colon.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Reactome Pathway
TNFs bind their physiological receptors (R-HSA-5669034 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
20 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 ligand superfamily member 15 (TNFSF15). [1]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [2]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [3]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [4]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [5]
Testosterone DM7HUNW Approved Testosterone increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [5]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [6]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [7]
Clozapine DMFC71L Approved Clozapine decreases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [8]
Malathion DMXZ84M Approved Malathion affects the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [9]
Menthol DMG2KW7 Approved Menthol decreases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [10]
Lucanthone DMZLBUO Approved Lucanthone increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [11]
PD-0325901 DM27D4J Phase 2 PD-0325901 decreases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [13]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [12]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin decreases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [14]
GW-3965 DMG60ET Investigative GW-3965 increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [15]
T0901317 DMZQVDI Investigative T0901317 increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [15]
25-hydroxycholesterol DMCHAQ7 Investigative 25-hydroxycholesterol increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [15]
24(S), 25-epoxycholesterol DMW2KI5 Investigative 24(S), 25-epoxycholesterol increases the expression of Tumor necrosis factor ligand superfamily member 15 (TNFSF15). [15]
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⏷ Show the Full List of 20 Drug(s)

References

1 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
3 Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
4 Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
5 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
6 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
7 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
8 Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T-cell responses. Immunology. 2007 Jun;121(2):266-75. doi: 10.1111/j.1365-2567.2007.02574.x. Epub 2007 Mar 7.
9 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
10 Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
11 Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
12 PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
13 Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.
14 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
15 LXR-activating oxysterols induce the expression of inflammatory markers in endothelial cells through LXR-independent mechanisms. Atherosclerosis. 2009 Nov;207(1):38-44.