Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT6L7U8)

• DOT Name: Interleukin-23 receptor (IL23R)
• Synonyms: IL-23 receptor; IL-23R
• Gene Name: IL23R
• UniProt ID: IL23R_HUMAN
• PDB ID: 5MZV; 6WDQ
• Sequence:
  MNQVTIQWDAVIALYILFSWCHGGITNINCSGHIWVEPATIFKMGMNISIYCQAAIKNCQ
  PRKLHFYKNGIKERFQITRINKTTARLWYKNFLEPHASMYCTAECPKHFQETLICGKDIS
  SGYPPDIPDEVTCVIYEYSGNMTCTWNAGKLTYIDTKYVVHVKSLETEEEQQYLTSSYIN
  ISTDSLQGGKKYLVWVQAANALGMEESKQLQIHLDDIVIPSAAVISRAETINATVPKTII
  YWDSQTTIEKVSCEMRYKATTNQTWNVKEFDTNFTYVQQSEFYLEPNIKYVFQVRCQETG
  KRYWQPWSSLFFHKTPETVPQVTSKAFQHDTWNSGLTVASISTGHLTSDNRGDIGLLLGM
  IVFAVMLSILSLIGIFNRSFRTGIKRRILLLIPKWLYEDIPNMKNSNVVKMLQENSELMN
  NNSSEQVLYVDPMITEIKEIFIPEHKPTDYKKENTGPLETRDYPQNSLFDNTTVVYIPDL
  NTGYKPQISNFLPEGSHLSNNNEITSLTLKPPVDSLDSGNNPRLQKHPNFAFSVSSVNSL
  SNTIFLGELSLILNQGECSSPDIQNSVEEETTMLLENDSPSETIPEQTLLPDEFVSCLGI
  VNEELPSINTYFPQNILESHFNRISLLEK
• Function: Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-Stat signaling cascade. IL23 functions in innate and adaptive immunity and may participate in acute response to infection in peripheral tissues. IL23 may be responsible for autoimmune inflammatory diseases and be important for tumorigenesis.
• Tissue Specificity: Expressed by monocytes, Th1, Th0, NK and dendritic cells. Isoform 1 is specifically expressed in NK cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
  Th17 cell differentiation (hsa04659)
  Pathways in cancer (hsa05200)
  Inflammatory bowel disease (hsa05321)
• Reactome Pathway:
  Interleukin-23 signaling (R-HSA-9020933)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Interleukin-23 receptor (IL23R) affects the response to substance of NAPQI.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interleukin-23 receptor (IL23R).	[1]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interleukin-23 receptor (IL23R).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-23 receptor (IL23R).	[4]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Interleukin-23 receptor (IL23R).	[5]
SGC-CBP30	DMTLRGZ	Investigative	SGC-CBP30 decreases the expression of Interleukin-23 receptor (IL23R).	[6]

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 increases the methylation of Interleukin-23 receptor (IL23R).	[3]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [3] 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.
• [4] Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression. Cell Rep. 2015 Sep 29;12(12):1986-96. doi: 10.1016/j.celrep.2015.08.046. Epub 2015 Sep 17.
• [5] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [6] CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10768-73. doi: 10.1073/pnas.1501956112. Epub 2015 Aug 10.
• [7] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.