Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT59OYXP)

• DOT Name: Interleukin-13 receptor subunit alpha-1 (IL13RA1)
• Synonyms: IL-13 receptor subunit alpha-1; IL-13R subunit alpha-1; IL-13R-alpha-1; IL-13RA1; Cancer/testis antigen 19; CT19; CD antigen CD213a1
• Gene Name: IL13RA1
• UniProt ID: I13R1_HUMAN
• PDB ID: 3BPN; 3BPO; 4HWB; 5E4E
• Pfam ID: PF18001 ; PF09240
• Sequence:
  MEWPARLCGLWALLLCAGGGGGGGGAAPTETQPPVTNLSVSVENLCTVIWTWNPPEGASS
  NCSLWYFSHFGDKQDKKIAPETRRSIEVPLNERICLQVGSQCSTNESEKPSILVEKCISP
  PEGDPESAVTELQCIWHNLSYMKCSWLPGRNTSPDTNYTLYYWHRSLEKIHQCENIFREG
  QYFGCSFDLTKVKDSSFEQHSVQIMVKDNAGKIKPSFNIVPLTSRVKPDPPHIKNLSFHN
  DDLYVQWENPQNFISRCLFYEVEVNNSQTETHNVFYVQEAKCENPEFERNVENTSCFMVP
  GVLPDTLNTVRIRVKTNKLCYEDDKLWSNWSQEMSIGKKRNSTLYITMLLIVPVIVAGAI
  IVLLLYLKRLKIIIFPPIPDPGKIFKEMFGDQNDDTLHWKKYDIYEKQTKEETDSVVLIE
  NLKKASQ
• Function: Binds with low affinity to interleukin-13 (IL13). Together with IL4RA can form a functional receptor for IL13. Also serves as an alternate accessory protein to the common cytokine receptor gamma chain for interleukin-4 (IL4) signaling, but cannot replace the function of IL2RG in allowing enhanced interleukin-2 (IL2) binding activity.
• Tissue Specificity: Ubiquitous. Highest levels in heart, liver, skeletal muscle and ovary; lowest levels in brain, lung and kidney. Also found in B-cells, T-cells and endothelial cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
  Pathways in cancer (hsa05200)
• Reactome Pathway: Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[11]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[14]
Tibolone	DM78XFG	Approved	Tibolone increases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[19]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interleukin-13 receptor subunit alpha-1 (IL13RA1).	[23]

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] 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.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [11] The DNA demethylating agent 5-aza-2'-deoxycytidine induces expression of NY-ESO-1 and other cancer/testis antigens in myeloid leukemia cells. Leuk Res. 2010 Jul;34(7):899-905. doi: 10.1016/j.leukres.2010.02.004. Epub 2010 Apr 10.
• [12] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [13] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women. Thromb Res. 2012 Jul;130(1):45-51. doi: 10.1016/j.thromres.2011.12.009. Epub 2012 Jan 2.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [18] 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.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [21] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [22] 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.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.