Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ4W7MT)

DOT Name Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B)
Synonyms Osteoclastogenesis inhibitory factor; Osteoprotegerin
Gene Name TNFRSF11B
Related Disease
Juvenile Paget disease ( )
UniProt ID
TR11B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3URF
Pfam ID
PF00531 ; PF00020
Sequence
MNNLLCCALVFLDISIKWTTQETFPPKYLHYDEETSHQLLCDKCPPGTYLKQHCTAKWKT
VCAPCPDHYYTDSWHTSDECLYCSPVCKELQYVKQECNRTHNRVCECKEGRYLEIEFCLK
HRSCPPGFGVVQAGTPERNTVCKRCPDGFFSNETSSKAPCRKHTNCSVFGLLLTQKGNAT
HDNICSGNSESTQKCGIDVTLCEEAFFRFAVPTKFTPNWLSVLVDNLPGTKVNAESVERI
KRQHSSQEQTFQLLKLWKHQNKDQDIVKKIIQDIDLCENSVQRHIGHANLTFEQLRSLME
SLPGKKVGAEDIEKTIKACKPSDQILKLLSLWRIKNGDQDTLKGLMHALKHSKTYHFPKT
VTQSLKKTIRFLHSFTMYKLYQKLFLEMIGNQVQSVKISCL
Function
Acts as a decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.
Tissue Specificity
Highly expressed in adult lung, heart, kidney, liver, spleen, thymus, prostate, ovary, small intestine, thyroid, lymph node, trachea, adrenal gland, testis, and bone marrow. Detected at very low levels in brain, placenta and skeletal muscle. Highly expressed in fetal kidney, liver and lung.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Osteoclast differentiation (hsa04380 )
Reactome Pathway
TNFs bind their physiological receptors (R-HSA-5669034 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Juvenile Paget disease DISNVDB2 Strong Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
46 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [6]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [7]
Quercetin DM3NC4M Approved Quercetin increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [8]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [10]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [11]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [12]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [14]
Progesterone DMUY35B Approved Progesterone decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [15]
Menadione DMSJDTY Approved Menadione increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [16]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [17]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [11]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [18]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [14]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [19]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [20]
DTI-015 DMXZRW0 Approved DTI-015 decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [21]
Menthol DMG2KW7 Approved Menthol decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [22]
Simvastatin DM30SGU Approved Simvastatin increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [23]
Gemcitabine DMSE3I7 Approved Gemcitabine increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [24]
Fenofibrate DMFKXDY Approved Fenofibrate decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [20]
Vitamin C DMXJ7O8 Approved Vitamin C decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [25]
Pamidronate DMB4AVP Approved Pamidronate increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [14]
Levonorgestrel DM1DP7T Approved Levonorgestrel increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [26]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [27]
Chondroitin sulfate DM0N19Y Phase 4 Chondroitin sulfate increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [28]
Ozagrel DMIGKA1 Phase 4 Ozagrel increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [29]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [11]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [30]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [31]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [32]
GSK2816126 DMJDVW4 Phase 1 GSK2816126 increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [33]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [34]
PMID26394986-Compound-22 DM43Z1G Patented PMID26394986-Compound-22 increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [35]
SB 203580 DMAET6F Terminated SB 203580 decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [36]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [37]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [38]
Paraquat DMR8O3X Investigative Paraquat increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [39]
Glyphosate DM0AFY7 Investigative Glyphosate increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [40]
U0126 DM31OGF Investigative U0126 decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [36]
Daidzein DMRFTJX Investigative Daidzein increases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [42]
carbocyclic thromboxane A2 DMGKSVF Investigative carbocyclic thromboxane A2 decreases the expression of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [29]
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⏷ Show the Full List of 46 Drug(s)
3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Methotrexate DM2TEOL Approved Methotrexate increases the secretion of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [13]
Sulfasalazine DMICA9H Approved Sulfasalazine increases the secretion of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [13]
D-glucose DMMG2TO Investigative D-glucose decreases the secretion of Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). [41]
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References

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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 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.
7 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.
8 Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
9 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.
10 Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
11 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.
12 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.
13 Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappaB, osteoprotegerin, and receptor activator of nuclear factor kappaB ligand. Arthritis Rheum. 2004 Dec;50(12):3831-43. doi: 10.1002/art.20637.
14 Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts. Biochem Biophys Res Commun. 2002 Mar 1;291(3):680-6. doi: 10.1006/bbrc.2002.6510.
15 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
16 Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by {gamma}-carboxylation-dependent and -independent mechanisms. Am J Physiol Cell Physiol. 2009 Dec;297(6):C1358-67. doi: 10.1152/ajpcell.00216.2009. Epub 2009 Aug 12.
17 Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
18 Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
19 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.
20 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
21 Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
22 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.
23 [Effect of simvastatin on the function of MG63 cell line]. Shanghai Kou Qiang Yi Xue. 2010 Dec;19(6):658-62.
24 Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
25 Induction of alkaline phosphatase activity by L-ascorbic acid in human osteoblastic cells: a potential role for CK2 and Ikaros. Nutrition. 2007 Oct;23(10):745-53. doi: 10.1016/j.nut.2007.06.013. Epub 2007 Jul 30.
26 [Effect of nylestriol and levonorgestrel on the expression of Opg/OPGL in human osteosarcoma MG-63 cell lines]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004 Dec;29(6):667-70.
27 Androgen decreases osteoprotegerin expression in prostate cancer cells. Prostate Cancer Prostatic Dis. 2007;10(2):160-6. doi: 10.1038/sj.pcan.4500927. Epub 2006 Dec 26.
28 Chondroitin and glucosamine sulfate in combination decrease the pro-resorptive properties of human osteoarthritis subchondral bone osteoblasts: a basic science study. Arthritis Res Ther. 2007;9(6):R117. doi: 10.1186/ar2325.
29 Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome). Nat Genet. 2008 Mar;40(3):284-6. doi: 10.1038/ng.2007.66. Epub 2008 Feb 10.
30 Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. Neoplasia. 2004 Jul-Aug;6(4):354-63. doi: 10.1593/neo.03478.
31 Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung. Toxicol Appl Pharmacol. 2017 Jun 1;324:1-11. doi: 10.1016/j.taap.2017.03.019. Epub 2017 Mar 27.
32 Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
33 Epigenetic control of skeletal development by the histone methyltransferase Ezh2. J Biol Chem. 2015 Nov 13;290(46):27604-17.
34 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.
35 Effects of celecoxib on the expression of osteoprotegerin, energy metabolism and cell viability in cultured human osteoblastic cells. Clin Exp Rheumatol. 2009 Jan-Feb;27(1):99-107.
36 Ovarian steroids, mitogen-activated protein kinases, and/or aspartic proteinases cooperate to control endometrial remodeling by regulating gene expression in the stroma and glands. Endocrinology. 2010 Sep;151(9):4515-26. doi: 10.1210/en.2009-1398. Epub 2010 Jul 21.
37 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
38 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.
39 Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways. J Toxicol Environ Health A. 2008;71(22):1457-67. doi: 10.1080/15287390802329364.
40 Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.
41 Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation. J Bone Miner Metab. 2010 May;28(3):276-88.
42 Daidzein increases OPG/RANKL ratio and suppresses IL-6 in MG-63 osteoblast cells. Int Immunopharmacol. 2016 Nov;40:32-40. doi: 10.1016/j.intimp.2016.08.014. Epub 2016 Aug 28.