Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5AN6ZR)

• DOT Name: Interleukin-10 receptor subunit beta (IL10RB)
• Synonyms: IL-10 receptor subunit beta; IL-10R subunit beta; IL-10RB; Cytokine receptor class-II member 4; Cytokine receptor family 2 member 4; CRF2-4; Interleukin-10 receptor subunit 2; IL-10R subunit 2; IL-10R2; CD antigen CDw210b
• Gene Name: IL10RB
• Related Disease:
  Inflammatory bowel disease 25
  Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome
• UniProt ID: I10R2_HUMAN
• PDB ID: 3LQM; 5T5W; 6X93
• Pfam ID: PF09294 ; PF01108
• Sequence:
  MAWSLGSWLGGCLLVSALGMVPPPENVRMNSVNFKNILQWESPAFAKGNLTFTAQYLSYR
  IFQDKCMNTTLTECDFSSLSKYGDHTLRVRAEFADEHSDWVNITFCPVDDTIIGPPGMQV
  EVLADSLHMRFLAPKIENEYETWTMKNVYNSWTYNVQYWKNGTDEKFQITPQYDFEVLRN
  LEPWTTYCVQVRGFLPDRNKAGEWSEPVCEQTTHDETVPSWMVAVILMASVFMVCLALLG
  CFALLWCVYKKTKYAFSPRNSLPQHLKEFLGHPHHNTLLFFSFPLSDENDVFDKLSVIAE
  DSESGKQNPGDSCSLGTPPGQGPQS
• Function: Shared cell surface receptor required for the activation of five class 2 cytokines: IL10, IL22, IL26, IL28, and IFNL1. The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  JAK-STAT sig.ling pathway (hsa04630)
  Toxoplasmosis (hsa05145)
  Tuberculosis (hsa05152)
  Human cytomegalovirus infection (hsa05163)
• Reactome Pathway:
  Interleukin-10 signaling (R-HSA-6783783)
  Interleukin-20 family signaling (R-HSA-8854691)
  Other interleukin signaling (R-HSA-449836)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inflammatory bowel disease 25	DISODKU2	Strong	Autosomal recessive	[1]
Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome	DISB2Y7L	Supportive	Autosomal recessive	[2]

13 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 Interleukin-10 receptor subunit beta (IL10RB).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Interleukin-10 receptor subunit beta (IL10RB).	[9]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Interleukin-10 receptor subunit beta (IL10RB).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[11]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[5]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Interleukin-10 receptor subunit beta (IL10RB).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Interleukin-10 receptor subunit beta (IL10RB).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Interleukin-10 receptor subunit beta (IL10RB).	[14]

References

• [1] Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 2009 Nov 19;361(21):2033-45. doi: 10.1056/NEJMoa0907206. Epub 2009 Nov 4.
• [2] Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy. Gastroenterology. 2012 Aug;143(2):347-55. doi: 10.1053/j.gastro.2012.04.045. Epub 2012 Apr 28.
• [3] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [6] 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.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Molecular mechanisms of action of angiopreventive anti-oxidants on endothelial cells: microarray gene expression analyses. Mutat Res. 2005 Dec 11;591(1-2):198-211.
• [13] 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.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.