Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPKSM49)

DOT Name Tumor necrosis factor receptor superfamily member 16 (NGFR)
Synonyms
Gp80-LNGFR; Low affinity neurotrophin receptor p75NTR; Low-affinity nerve growth factor receptor; NGF receptor; Low-affinity nerve growth factor receptor p75NGFR; Low-affinity nerve growth factor receptor p75NGR; p75 ICD; CD antigen CD271
Gene Name NGFR
UniProt ID
TNR16_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2N80; 2N83; 2N97; 3EWV; 5ZGG; 7CSQ
Pfam ID
PF00531 ; PF18422 ; PF00020
Sequence
MGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGAN
QTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTG
RCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLREC
TRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQ
PVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNSCKQNKQGANSRPVNQTPPPEGEK
LHSDSGISVDSQSLHDQQPHTQTASGQALKGDGGLYSSLPPAKREEVEKLLNGSAGDTWR
HLAGELGYQPEHIDSFTHEACPVRALLASWATQDSATLDALLAALRRIQRADLVESLCSE
STATSPV
Function
Low affinity receptor which can bind to NGF, BDNF, NTF3, and NTF4. Forms a heterodimeric receptor with SORCS2 that binds the precursor forms of NGF, BDNF and NTF3 with high affinity, and has much lower affinity for mature NGF and BDNF. Plays an important role in differentiation and survival of specific neuronal populations during development. Can mediate cell survival as well as cell death of neural cells. Plays a role in the inactivation of RHOA. Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake. Necessary for the circadian oscillation of the clock genes BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SCmgetaN) of the brain and in liver and of the genes involved in glucose and lipid metabolism in the liver.
KEGG Pathway
Virion - Ebolavirus and Lyssavirus (hsa03265 )
MAPK sig.ling pathway (hsa04010 )
Ras sig.ling pathway (hsa04014 )
Rap1 sig.ling pathway (hsa04015 )
Cytokine-cytokine receptor interaction (hsa04060 )
PI3K-Akt sig.ling pathway (hsa04151 )
Apoptosis - multiple species (hsa04215 )
Neurotrophin sig.ling pathway (hsa04722 )
Transcriptio.l misregulation in cancer (hsa05202 )
Reactome Pathway
NRAGE signals death through JNK (R-HSA-193648 )
p75NTR negatively regulates cell cycle via SC1 (R-HSA-193670 )
Ceramide signalling (R-HSA-193681 )
Regulated proteolysis of p75NTR (R-HSA-193692 )
NFG and proNGF binds to p75NTR (R-HSA-205017 )
NADE modulates death signalling (R-HSA-205025 )
NRIF signals cell death from the nucleus (R-HSA-205043 )
p75NTR recruits signalling complexes (R-HSA-209543 )
NF-kB is activated and signals survival (R-HSA-209560 )
Axonal growth stimulation (R-HSA-209563 )
Axonal growth inhibition (RHOA activation) (R-HSA-193634 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
36 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 16 (NGFR). [1]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [2]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [7]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [8]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [9]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [10]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [8]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [11]
Ethanol DMDRQZU Approved Ethanol increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [12]
Aspirin DM672AH Approved Aspirin increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [13]
Nicotine DMWX5CO Approved Nicotine increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [14]
Menthol DMG2KW7 Approved Menthol increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [15]
Ibuprofen DM8VCBE Approved Ibuprofen increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [13]
Flurbiprofen DMGN4BY Approved Flurbiprofen increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [13]
Naproxen DMZ5RGV Approved Naproxen increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [16]
Ketoprofen DMRKXPT Approved Ketoprofen increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [16]
Trametinib DM2JGQ3 Approved Trametinib increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [17]
Fenoprofen DML5VQ0 Approved Fenoprofen increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [16]
Oxaprozin DM9UB0P Approved Oxaprozin increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [16]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [18]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [19]
Curcumin DMQPH29 Phase 3 Curcumin decreases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [20]
EXISULIND DMBY56U Phase 3 EXISULIND increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [13]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [21]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [2]
PMID26394986-Compound-22 DM43Z1G Patented PMID26394986-Compound-22 increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [13]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [22]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [23]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [24]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [25]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of Tumor necrosis factor receptor superfamily member 16 (NGFR). [26]
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⏷ Show the Full List of 36 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 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
3 TAp73 knockout mice show morphological and functional nervous system defects associated with loss of p75 neurotrophin receptor. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18952-7. doi: 10.1073/pnas.1221172110. Epub 2013 Nov 4.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
5 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.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
8 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.
9 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
10 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
11 Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
12 Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
13 A comparison of the effectiveness of selected non-steroidal anti-inflammatory drugs and their derivatives against cancer cells in vitro. Cancer Chemother Pharmacol. 2008 Feb;61(2):203-14. doi: 10.1007/s00280-007-0462-3. Epub 2007 Apr 20.
14 Long term effects of cigarette smoke extract or nicotine on nerve growth factor and its receptors in a bronchial epithelial cell line. Toxicol In Vitro. 2018 Dec;53:29-36. doi: 10.1016/j.tiv.2018.07.020. Epub 2018 Aug 1.
15 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.
16 The aryl propionic acid R-flurbiprofen selectively induces p75NTR-dependent decreased survival of prostate tumor cells. Cancer Res. 2007 Apr 1;67(7):3254-62.
17 Harnessing autophagy to overcome mitogen-activated protein kinase kinase inhibitor-induced resistance in metastatic melanoma. Br J Dermatol. 2019 Feb;180(2):346-356. doi: 10.1111/bjd.17333. Epub 2018 Nov 25.
18 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
19 Quantitative nuclear proteomics identifies that miR-137-mediated EZH2 reduction regulates resveratrol-induced apoptosis of neuroblastoma cells. Mol Cell Proteomics. 2015 Feb;14(2):316-28. doi: 10.1074/mcp.M114.041905. Epub 2014 Dec 11.
20 Curcumin suppresses the stemness of non-small cell lung cancer cells via promoting the nuclear-cytoplasm translocation of TAZ. Environ Toxicol. 2021 Jun;36(6):1135-1142. doi: 10.1002/tox.23112. Epub 2021 Feb 4.
21 Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
22 The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
23 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.
24 Anticarcinogenic activities of sulforaphane are influenced by Nerve Growth Factor in human melanoma A375 cells. Food Chem Toxicol. 2018 Mar;113:154-161. doi: 10.1016/j.fct.2018.01.051. Epub 2018 Jan 31.
25 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.
26 Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.