Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0G7E35)

• DOT Name: Interleukin-1 receptor type 2 (IL1R2)
• Synonyms: IL-1R-2; IL-1RT-2; IL-1RT2; CD121 antigen-like family member B; CDw121b; IL-1 type II receptor; Interleukin-1 receptor beta; IL-1R-beta; Interleukin-1 receptor type II; CD antigen CD121b
• Gene Name: IL1R2
• UniProt ID: IL1R2_HUMAN
• PDB ID: 3O4O
• Pfam ID: PF00047
• Sequence:
  MLRLYVLVMGVSAFTLQPAAHTGAARSCRFRGRHYKREFRLEGEPVALRCPQVPYWLWAS
  VSPRINLTWHKNDSARTVPGEEETRMWAQDGALWLLPALQEDSGTYVCTTRNASYCDKMS
  IELRVFENTDAFLPFISYPQILTLSTSGVLVCPDLSEFTRDKTDVKIQWYKDSLLLDKDN
  EKFLSVRGTTHLLVHDVALEDAGYYRCVLTFAHEGQQYNITRSIELRIKKKKEETIPVII
  SPLKTISASLGSRLTIPCKVFLGTGTPLTTMLWWTANDTHIESAYPGGRVTEGPRQEYSE
  NNENYIEVPLIFDPVTREDLHMDFKCVVHNTLSFQTLRTTVKEASSTFSWGIVLAPLSLA
  FLVLGGIWMHRRCKHRTGKADGLTVLWPHHQDFQSYPK
• Function: Non-signaling receptor for IL1A, IL1B and IL1RN. Reduces IL1B activities. Serves as a decoy receptor by competitive binding to IL1B and preventing its binding to IL1R1. Also modulates cellular response through non-signaling association with IL1RAP after binding to IL1B. IL1R2 (membrane and secreted forms) preferentially binds IL1B and poorly IL1A and IL1RN. The secreted IL1R2 recruits secreted IL1RAP with high affinity; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Hematopoietic cell lineage (hsa04640)
  Amoebiasis (hsa05146)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Transcriptio.l misregulation in cancer (hsa05202)
  Prostate cancer (hsa05215)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Interleukin-1 signaling (R-HSA-9020702)
  Interleukin-10 signaling (R-HSA-6783783)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Interleukin-1 receptor type 2 (IL1R2) affects the response to substance of Aspirin.	[26]
Capecitabine	DMTS85L	Approved	Interleukin-1 receptor type 2 (IL1R2) increases the response to substance of Capecitabine.	[27]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Interleukin-1 receptor type 2 (IL1R2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interleukin-1 receptor type 2 (IL1R2).	[20]

28 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Interleukin-1 receptor type 2 (IL1R2).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Interleukin-1 receptor type 2 (IL1R2).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[12]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[14]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[15]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[16]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[4]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[21]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Interleukin-1 receptor type 2 (IL1R2).	[24]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[25]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[16]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[16]
Farnesol	DMV2X1B	Investigative	Farnesol increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[16]
benzyl bromide	DM857X2	Investigative	benzyl bromide increases the expression of Interleukin-1 receptor type 2 (IL1R2).	[22]

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] 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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Aberrantly expressed genes in HaCaT keratinocytes chronically exposed to arsenic trioxide. Biomark Insights. 2011 Feb 8;6:7-16.
• [7] 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.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] 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.
• [12] Sulfur mustard alkylates steroid hormones and impacts hormone function in vitro. Arch Toxicol. 2019 Nov;93(11):3141-3152. doi: 10.1007/s00204-019-02571-x. Epub 2019 Sep 12.
• [13] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] 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.
• [16] The THP-1 cell toolbox: a new concept integrating the key events of skin sensitization. Arch Toxicol. 2019 Apr;93(4):941-951.
• [17] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] 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.
• [20] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [21] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [22] Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes. Toxicol Lett. 2010 Nov 10;199(1):51-9.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [26] Gene-expression profiles in human nasal polyp tissues and identification of genetic susceptibility in aspirin-intolerant asthma. Clin Exp Allergy. 2009 Jul;39(7):972-81. doi: 10.1111/j.1365-2222.2009.03229.x. Epub 2009 Mar 27.
• [27] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.