Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTU8959)

DOT Name Interleukin-1 receptor type 1 (IL1R1)
Synonyms IL-1R-1; IL-1RT-1; IL-1RT1; EC 3.2.2.6; CD121 antigen-like family member A; Interleukin-1 receptor alpha; IL-1R-alpha; Interleukin-1 receptor type I; p80; CD antigen CD121a
Gene Name IL1R1
UniProt ID
IL1R1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1G0Y; 1IRA; 1ITB; 4DEP; 4GAF
EC Number
3.2.2.6
Pfam ID
PF13895 ; PF18452 ; PF01582
Sequence
MKVLLRLICFIALLISSLEADKCKEREEKIILVSSANEIDVRPCPLNPNEHKGTITWYKD
DSKTPVSTEQASRIHQHKEKLWFVPAKVEDSGHYYCVVRNSSYCLRIKISAKFVENEPNL
CYNAQAIFKQKLPVAGDGGLVCPYMEFFKNENNELPKLQWYKDCKPLLLDNIHFSGVKDR
LIVMNVAEKHRGNYTCHASYTYLGKQYPITRVIEFITLEENKPTRPVIVSPANETMEVDL
GSQIQLICNVTGQLSDIAYWKWNGSVIDEDDPVLGEDYYSVENPANKRRSTLITVLNISE
IESRFYKHPFTCFAKNTHGIDAAYIQLIYPVTNFQKHMIGICVTLTVIIVCSVFIYKIFK
IDIVLWYRDSCYDFLPIKASDGKTYDAYILYPKTVGEGSTSDCDIFVFKVLPEVLEKQCG
YKLFIYGRDDYVGEDIVEVINENVKKSRRLIIILVRETSGFSWLGGSSEEQIAMYNALVQ
DGIKVVLLELEKIQDYEKMPESIKFIKQKHGAIRWSGDFTQGPQSAKTRFWKNVRYHMPV
QRRSPSSKHQLLSPATKEKLQREAHVPLG
Function
Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the coreceptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Binds ligands with comparable affinity and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling complex. Involved in IL1B-mediated costimulation of IFNG production from T-helper 1 (Th1) cells.
Tissue Specificity Expressed in T-helper cell subsets. Preferentially expressed in T-helper 1 (Th1) cells.
KEGG Pathway
MAPK sig.ling pathway (hsa04010 )
Cytokine-cytokine receptor interaction (hsa04060 )
NF-kappa B sig.ling pathway (hsa04064 )
Osteoclast differentiation (hsa04380 )
Hematopoietic cell lineage (hsa04640 )
Th17 cell differentiation (hsa04659 )
Inflammatory mediator regulation of TRP channels (hsa04750 )
Pathogenic Escherichia coli infection (hsa05130 )
Shigellosis (hsa05131 )
Amoebiasis (hsa05146 )
Human cytomegalovirus infection (hsa05163 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
Interleukin-1 signaling (R-HSA-9020702 )
Potential therapeutics for SARS (R-HSA-9679191 )
Interleukin-10 signaling (R-HSA-6783783 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Temozolomide DMKECZD Approved Interleukin-1 receptor type 1 (IL1R1) affects the response to substance of Temozolomide. [39]
DTI-015 DMXZRW0 Approved Interleukin-1 receptor type 1 (IL1R1) affects the response to substance of DTI-015. [39]
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41 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 Interleukin-1 receptor type 1 (IL1R1). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Interleukin-1 receptor type 1 (IL1R1). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [7]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [8]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Interleukin-1 receptor type 1 (IL1R1). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Interleukin-1 receptor type 1 (IL1R1). [11]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [12]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [13]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Interleukin-1 receptor type 1 (IL1R1). [14]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Interleukin-1 receptor type 1 (IL1R1). [15]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Interleukin-1 receptor type 1 (IL1R1). [16]
Progesterone DMUY35B Approved Progesterone increases the expression of Interleukin-1 receptor type 1 (IL1R1). [17]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Interleukin-1 receptor type 1 (IL1R1). [19]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [20]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Interleukin-1 receptor type 1 (IL1R1). [21]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [22]
Paclitaxel DMLB81S Approved Paclitaxel decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [23]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Interleukin-1 receptor type 1 (IL1R1). [14]
Dasatinib DMJV2EK Approved Dasatinib decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [24]
Thalidomide DM70BU5 Approved Thalidomide decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [25]
Diphenylpyraline DMW4X37 Approved Diphenylpyraline increases the expression of Interleukin-1 receptor type 1 (IL1R1). [26]
Dinoprostone DMTYOPD Approved Dinoprostone increases the expression of Interleukin-1 receptor type 1 (IL1R1). [27]
Lenalidomide DM6Q7U4 Approved Lenalidomide decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [25]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Interleukin-1 receptor type 1 (IL1R1). [28]
Bardoxolone methyl DMODA2X Phase 3 Bardoxolone methyl affects the expression of Interleukin-1 receptor type 1 (IL1R1). [29]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of Interleukin-1 receptor type 1 (IL1R1). [30]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [31]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [32]
PMID27336223-Compound-5 DM6E50A Patented PMID27336223-Compound-5 decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [22]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Interleukin-1 receptor type 1 (IL1R1). [33]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Interleukin-1 receptor type 1 (IL1R1). [34]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [35]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [36]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [37]
ELLAGIC ACID DMX8BS5 Investigative ELLAGIC ACID decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [38]
Chrysin DM7V2LG Investigative Chrysin decreases the expression of Interleukin-1 receptor type 1 (IL1R1). [38]
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⏷ Show the Full List of 41 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Interleukin-1 receptor type 1 (IL1R1). [18]
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References

1 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
2 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
3 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.
4 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.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
8 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.
9 Genome-wide analysis of BEAS-2B cells exposed to trivalent arsenicals and dimethylthioarsinic acid. Toxicology. 2010 Jan 31;268(1-2):31-9.
10 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.
11 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
12 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
13 Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
14 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
15 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
16 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.
17 Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
18 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
19 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
20 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.
21 Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells. Br J Cancer. 2007 Oct 22;97(8):1099-105. doi: 10.1038/sj.bjc.6604003. Epub 2007 Sep 25.
22 PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
23 Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
24 Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation. Blood. 2008 Feb 1;111(3):1366-77. doi: 10.1182/blood-2007-04-084814. Epub 2007 Oct 25.
25 Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood. 2005 Apr 15;105(8):3286-94. doi: 10.1182/blood-2004-06-2101. Epub 2004 Dec 23.
26 Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
27 Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med. 2009 Mar 16;206(3):535-48. doi: 10.1084/jem.20082293. Epub 2009 Mar 9.
28 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
29 Fluorescent tagging of endogenous Heme oxygenase-1 in human induced pluripotent stem cells for high content imaging of oxidative stress in various differentiated lineages. Arch Toxicol. 2021 Oct;95(10):3285-3302. doi: 10.1007/s00204-021-03127-8. Epub 2021 Sep 4.
30 Expression of neutrophil SOD2 is reduced after lipopolysaccharide stimulation: a potential cause of neutrophil dysfunction in chronic kidney disease. Nephrol Dial Transplant. 2011 Jul;26(7):2195-201. doi: 10.1093/ndt/gfq673. Epub 2010 Nov 2.
31 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
32 Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression. Cell Rep. 2015 Sep 29;12(12):1986-96. doi: 10.1016/j.celrep.2015.08.046. Epub 2015 Sep 17.
33 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
34 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.
35 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
36 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
37 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
38 Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact. 2010 Dec 5;188(3):659-67.
39 Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.