Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT6YSKM)

• DOT Name: Interleukin-7 (IL7)
• Synonyms: IL-7
• Gene Name: IL7
• Related Disease: Epidermodysplasia verruciformis
• UniProt ID: IL7_HUMAN
• PDB ID: 3DI2; 3DI3
• Pfam ID: PF01415
• Sequence:
  MFHVSFRYIFGLPPLILVLLPVASSDCDIEGKDGKQYESVLMVSIDQLLDSMKEIGSNCL
  NNEFNFFKRHICDANKEGMFLFRAARKLRQFLKMNSTGDFDLHLLKVSEGTTILLNCTGQ
  VKGRKPAALGEAQPTKSLEENKSLKEQKKLNDLCFLKRLLQEIKTCWNKILMGTKEH
• Function: Hematopoietic cytokine that plays an essential role in the development, expansion, and survival of naive and memory T-cells and B-cells thereby regulating the number of mature lymphocytes and maintaining lymphoid homeostasis. Mechanistically, exerts its biological effects through a receptor composed of IL7RA subunit and the cytokine receptor common subunit gamma/CSF2RG. Binding to the receptor leads to activation of various kinases including JAK1 or JAK3 depending on the cell type and subsequently propagation of signals through activation of several downstream signaling pathways including the PI3K/Akt/mTOR or the JAK-STAT5.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt sig.ling pathway (hsa04151)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Pathways in cancer (hsa05200)
• Reactome Pathway: Interleukin-7 signaling (R-HSA-1266695)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epidermodysplasia verruciformis	DIS54WBS	Supportive	Autosomal recessive	[1]

1 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-7 (IL7).	[2]

22 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-7 (IL7).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Interleukin-7 (IL7).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-7 (IL7).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Interleukin-7 (IL7).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Interleukin-7 (IL7).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Interleukin-7 (IL7).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Interleukin-7 (IL7).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Interleukin-7 (IL7).	[10]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interleukin-7 (IL7).	[11]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Interleukin-7 (IL7).	[8]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Interleukin-7 (IL7).	[12]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Interleukin-7 (IL7).	[13]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of Interleukin-7 (IL7).	[15]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Interleukin-7 (IL7).	[16]
Oxymetholone	DMFXUT8	Approved	Oxymetholone increases the expression of Interleukin-7 (IL7).	[17]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Interleukin-7 (IL7).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Interleukin-7 (IL7).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-7 (IL7).	[19]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Interleukin-7 (IL7).	[20]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Interleukin-7 (IL7).	[21]
Manganese	DMKT129	Investigative	Manganese increases the expression of Interleukin-7 (IL7).	[22]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Interleukin-7 (IL7).	[23]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the secretion of Interleukin-7 (IL7).	[14]

References

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• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh. Toxicol Lett. 2009 Mar 28;185(3):197-202. doi: 10.1016/j.toxlet.2009.01.001. Epub 2009 Jan 9.
• [7] 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.
• [8] Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC). Front Microbiol. 2015 Dec 22;6:1452. doi: 10.3389/fmicb.2015.01452. eCollection 2015.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [12] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [13] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [14] Zinc induces chemokine and inflammatory cytokine release from human promonocytes. J Hazard Mater. 2011 Nov 30;196:335-41. doi: 10.1016/j.jhazmat.2011.09.035. Epub 2011 Sep 19.
• [15] Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes. Chem Biol Interact. 2016 Aug 5;255:31-44.
• [16] Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo. Toxicol Appl Pharmacol. 2014 Jan 15;274(2):302-12.
• [17] Direct and indirect effects of androgens on survival of hematopoietic progenitor cells in vitro. J Korean Med Sci. 2005 Jun;20(3):409-16. doi: 10.3346/jkms.2005.20.3.409.
• [18] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [19] BET inhibition as a single or combined therapeutic approach in primary paediatric B-precursor acute lymphoblastic leukaemia. Blood Cancer J. 2013 Jul 19;3(7):e126. doi: 10.1038/bcj.2013.24.
• [20] Paraquat exposure induces Parkinsonism by altering lipid profile and evoking neuroinflammation in the midbrain. Environ Int. 2022 Nov;169:107512. doi: 10.1016/j.envint.2022.107512. Epub 2022 Sep 8.
• [21] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [22] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [23] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.