Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0LF3D7)

• DOT Name: Interleukin-27 subunit beta (EBI3)
• Synonyms: IL-27 subunit beta; IL-27B; Epstein-Barr virus-induced gene 3 protein; EBV-induced gene 3 protein
• Gene Name: EBI3
• UniProt ID: IL27B_HUMAN
• PDB ID: 7U7N; 7ZXK; 8D85
• Pfam ID: PF00041
• Sequence:
  MTPQLLLALVLWASCPPCSGRKGPPAALTLPRVQCRASRYPIAVDCSWTLPPAPNSTSPV
  SFIATYRLGMAARGHSWPCLQQTPTSTSCTITDVQLFSMAPYVLNVTAVHPWGSSSSFVP
  FITEHIIKPDPPEGVRLSPLAERQLQVQWEPPGSWPFPEIFSLKYWIRYKRQGAARFHRV
  GPIEATSFILRAVRPRARYYVQVAAQDLTDYGELSDWSLPATATMSLGK
• Function: Associates with IL27 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive but not memory CD4 T-cells. It also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Th17 cell differentiation (hsa04659)
• Reactome Pathway:
  Interleukin-27 signaling (R-HSA-9020956)
  Interleukin-35 Signalling (R-HSA-8984722)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-27 subunit beta (EBI3).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interleukin-27 subunit beta (EBI3).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interleukin-27 subunit beta (EBI3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-27 subunit beta (EBI3).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Interleukin-27 subunit beta (EBI3).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Interleukin-27 subunit beta (EBI3).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Interleukin-27 subunit beta (EBI3).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Interleukin-27 subunit beta (EBI3).	[8]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Interleukin-27 subunit beta (EBI3).	[9]
Epanova	DMHEAGL	Approved	Epanova increases the expression of Interleukin-27 subunit beta (EBI3).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Interleukin-27 subunit beta (EBI3).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Interleukin-27 subunit beta (EBI3).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-27 subunit beta (EBI3).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Interleukin-27 subunit beta (EBI3).	[15]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Interleukin-27 subunit beta (EBI3).	[16]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid decreases the expression of Interleukin-27 subunit beta (EBI3).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Interleukin-27 subunit beta (EBI3).	[14]

References

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• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Dec;334:113466. doi: 10.1016/j.expneurol.2020.113466. Epub 2020 Sep 17.
• [6] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells. J Immunol. 2011 Aug 15;187(4):1778-87. doi: 10.4049/jimmunol.1003919. Epub 2011 Jul 18.
• [9] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [10] Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells. Breast Cancer Res Treat. 2007 Jan;101(1):7-16. doi: 10.1007/s10549-006-9269-x. Epub 2006 Jul 6.
• [11] 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.
• [12] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] 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.
• [15] 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.
• [16] IL-27 Production and Regulation in Human Dendritic Cells Treated with the Chemical Sensitizer NiSO(4). Chem Res Toxicol. 2018 Dec 17;31(12):1323-1331. doi: 10.1021/acs.chemrestox.8b00203. Epub 2018 Nov 27.
• [17] The impact on T-regulatory cell related immune responses in rural women exposed to polycyclic aromatic hydrocarbons (PAHs) in household air pollution in Gansu, China: A pilot investigation. Environ Res. 2019 Jun;173:306-317. doi: 10.1016/j.envres.2019.03.053. Epub 2019 Mar 26.