Details of Drug Off-Target (DOT)

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

DOT Name	Interferon lambda-3 (IFNL3)
Synonyms	IFN-lambda-3; Cytokine Zcyto22; Interleukin-28B; IL-28B; Interleukin-28C; IL-28C
Gene Name	IFNL3
UniProt ID	IFNL3_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3HHC; 5T5W
Pfam ID	PF15177
Sequence	MTGDCMPVLVLMAAVLTVTGAVPVARLRGALPDARGCHIAQFKSLSPQELQAFKRAKDAL EESLLLKDCKCRSRLFPRTWDLRQLQVRERPVALEAELALTLKVLEATADTDPALGDVLD QPLHTLHHILSQLRACIQPQPTAGPRTRGRLHHWLHRLQEAPKKESPGCLEASVTFNLFR LLTRDLNCVASGDLCV
Function	Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression.
KEGG Pathway	Cytokine-cytokine receptor interaction (hsa04060 ) JAK-STAT sig.ling pathway (hsa04630 )
Reactome Pathway	Interleukin-20 family signaling (R-HSA-8854691 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Peginterferon alfa-2b	DMAP58Y	Approved	Interferon lambda-3 (IFNL3) decreases the response of Peginterferon alfa-2b.	[3]
Peginterferon alfa-2a	DMJI3BA	Approved	Interferon lambda-3 (IFNL3) decreases the response of Peginterferon alfa-2a.	[3]
Ribavirin	DMEYLH9	Phase 1 Trial	Interferon lambda-3 (IFNL3) decreases the response of Ribavirin.	[3]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Interferon lambda-3 (IFNL3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Interferon lambda-3 (IFNL3).	[2]
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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	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.
3	Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon--based regimens. Clin Pharmacol Ther. 2014 Feb;95(2):141-6. doi: 10.1038/clpt.2013.203. Epub 2013 Oct 4.