Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHFXK95)

• DOT Name: Interleukin-20 receptor subunit beta (IL20RB)
• Synonyms: IL-20 receptor subunit beta; IL-20R-beta; IL-20RB; Fibronectin type III domain containing 6; FNDC6; IL-20R2
• Gene Name: IL20RB
• Related Disease:
  Glaucoma/ocular hypertension
  Autoimmune disease
  Clear cell renal carcinoma
  Non-small-cell lung cancer
  OPTN-related open angle glaucoma
  Psoriasis
  Vitiligo
  Melanoma
• UniProt ID: I20RB_HUMAN
• PDB ID: 4DOH; 6DF3
• Pfam ID: PF09294 ; PF01108
• Sequence:
  MQTFTMVLEEIWTSLFMWFFYALIPCLLTDEVAILPAPQNLSVLSTNMKHLLMWSPVIAP
  GETVYYSVEYQGEYESLYTSHIWIPSSWCSLTEGPECDVTDDITATVPYNLRVRATLGSQ
  TSAWSILKHPFNRNSTILTRPGMEITKDGFHLVIELEDLGPQFEFLVAYWRREPGAEEHV
  KMVRSGGIPVHLETMEPGAAYCVKAQTFVKAIGRYSAFSQTECVEVQGEAIPLVLALFAF
  VGFMLILVVVPLFVWKMGRLLQYSCCPVVVLPDTLKITNSPQKLISCRREEVDACATAVM
  SPEELLRAWIS
• Function: The IL20RA/IL20RB dimer is a receptor for IL19, IL20 and IL24. The IL22RA1/IL20RB dimer is a receptor for IL20 and IL24.
• Tissue Specificity: Widely expressed with highest levels in skin and testis. Highly expressed in psoriatic skin.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: Interleukin-20 family signaling (R-HSA-8854691)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glaucoma/ocular hypertension	DISLBXBY	Definitive	Genetic Variation	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
OPTN-related open angle glaucoma	DISDR98A	Strong	Genetic Variation	[1]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[5]
Vitiligo	DISR05SL	Strong	Altered Expression	[6]
Melanoma	DIS1RRCY	moderate	Biomarker	[7]

20 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-20 receptor subunit beta (IL20RB).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Interleukin-20 receptor subunit beta (IL20RB).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Interleukin-20 receptor subunit beta (IL20RB).	[16]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[17]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[18]
Palbociclib	DMD7L94	Approved	Palbociclib increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[15]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[22]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Interleukin-20 receptor subunit beta (IL20RB).	[23]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Interleukin-20 receptor subunit beta (IL20RB).	[24]

1 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-20 receptor subunit beta (IL20RB).	[21]

References

• [1] The Role of the IL-20 Subfamily in Glaucoma.Mediators Inflamm. 2016;2016:4083735. doi: 10.1155/2016/4083735. Epub 2016 Jan 20.
• [2] IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis.J Immunol. 2010 Feb 15;184(4):1793-8. doi: 10.4049/jimmunol.0901829. Epub 2010 Jan 8.
• [3] Bioinformatics Analysis Suggests the Combined Expression of AURKB and KIF18B Being an Important Event in the Development of Clear Cell Renal Cell Carcinoma.Pathol Oncol Res. 2020 Jul;26(3):1583-1594. doi: 10.1007/s12253-019-00740-y. Epub 2019 Sep 5.
• [4] IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF.Eur J Cancer. 2011 Aug;47(12):1908-18. doi: 10.1016/j.ejca.2011.04.012. Epub 2011 May 10.
• [5] Association analysis of IL20RA and IL20RB genes in psoriasis.Genes Immun. 2008 Jul;9(5):445-51. doi: 10.1038/gene.2008.36. Epub 2008 May 15.
• [6] Association analysis of genes of the IL19 cluster and their receptors in vitiligo patients.Dermatology. 2010;221(3):261-6. doi: 10.1159/000317526.
• [7] Combination of adenoviruses expressing melanoma differentiation-associated gene-7 and chemotherapeutic agents produces enhanced cytotoxicity on esophageal carcinoma.Cancer Gene Ther. 2014 Jan;21(1):31-7. doi: 10.1038/cgt.2013.79. Epub 2014 Jan 17.
• [8] 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.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] 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.
• [13] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [18] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [19] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] 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.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [24] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.