Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGI4NSA)

• DOT Name: Interleukin-2 (IL2)
• Synonyms: IL-2; T-cell growth factor; TCGF; Aldesleukin
• Gene Name: IL2
• UniProt ID: IL2_HUMAN
• PDB ID: 1IRL; 1M47; 1M48; 1M49; 1M4A; 1M4B; 1M4C; 1NBP; 1PW6; 1PY2; 1QVN; 1Z92; 2B5I; 2ERJ; 3INK; 3QAZ; 3QB1; 4NEJ; 4NEM; 5LQB; 5M5E; 5UTZ; 6LX3; 6LXW; 6VWU; 6YE3; 7DR4; 7M2G; 7RA9; 7RAA; 7YZJ; 7ZMZ
• Pfam ID: PF00715
• Sequence:
  MYRMQLLSCIALSLALVTNSAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRML
  TFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSE
  TTFMCEYADETATIVEFLNRWITFCQSIISTLT
• Function: Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance. Binds to a receptor complex composed of either the high-affinity trimeric IL-2R (IL2RA/CD25, IL2RB/CD122 and IL2RG/CD132) or the low-affinity dimeric IL-2R (IL2RB and IL2RG). Interaction with the receptor leads to oligomerization and conformation changes in the IL-2R subunits resulting in downstream signaling starting with phosphorylation of JAK1 and JAK3. In turn, JAK1 and JAK3 phosphorylate the receptor to form a docking site leading to the phosphorylation of several substrates including STAT5. This process leads to activation of several pathways including STAT, phosphoinositide-3-kinase/PI3K and mitogen-activated protein kinase/MAPK pathways. Functions as a T-cell growth factor and can increase NK-cell cytolytic activity as well. Promotes strong proliferation of activated B-cells and subsequently immunoglobulin production. Plays a pivotal role in regulating the adaptive immune system by controlling the survival and proliferation of regulatory T-cells, which are required for the maintenance of immune tolerance. Moreover, participates in the differentiation and homeostasis of effector T-cell subsets, including Th1, Th2, Th17 as well as memory CD8-positive T-cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  PI3K-Akt sig.ling pathway (hsa04151)
  C-type lectin receptor sig.ling pathway (hsa04625)
  JAK-STAT sig.ling pathway (hsa04630)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  T cell receptor sig.ling pathway (hsa04660)
  Intesti.l immune network for IgA production (hsa04672)
  Type I diabetes mellitus (hsa04940)
  Yersinia infection (hsa05135)
  Chagas disease (hsa05142)
  Measles (hsa05162)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Autoimmune thyroid disease (hsa05320)
  Inflammatory bowel disease (hsa05321)
  Allograft rejection (hsa05330)
  Graft-versus-host disease (hsa05332)
• Reactome Pathway:
  RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) (R-HSA-8877330)
  Interleukin-2 signaling (R-HSA-9020558)
  Interleukin receptor SHC signaling (R-HSA-912526)
  RAF/MAP kinase cascade (R-HSA-5673001)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Lovastatin	DM9OZWQ	Approved	Interleukin-2 (IL2) increases the Cell-mediated cytotoxicity ADR of Lovastatin.	[40]
Sirolimus	DMGW1ID	Approved	Interleukin-2 (IL2) increases the Nephropathy toxic ADR of Sirolimus.	[40]

37 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-2 (IL2).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Interleukin-2 (IL2).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interleukin-2 (IL2).	[3]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Interleukin-2 (IL2).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-2 (IL2).	[6]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Interleukin-2 (IL2).	[7]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Interleukin-2 (IL2).	[9]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Interleukin-2 (IL2).	[10]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Interleukin-2 (IL2).	[1]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Interleukin-2 (IL2).	[11]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of Interleukin-2 (IL2).	[12]
Melatonin	DMKWFBT	Approved	Melatonin increases the activity of Interleukin-2 (IL2).	[13]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Interleukin-2 (IL2).	[14]
Morphine	DMRMS0L	Approved	Morphine decreases the expression of Interleukin-2 (IL2).	[15]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid decreases the expression of Interleukin-2 (IL2).	[16]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the expression of Interleukin-2 (IL2).	[17]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid affects the expression of Interleukin-2 (IL2).	[16]
Methadone	DMTW6IU	Approved	Methadone decreases the expression of Interleukin-2 (IL2).	[15]
Fentanyl	DM8WAHT	Approved	Fentanyl decreases the expression of Interleukin-2 (IL2).	[15]
Betamethasone valerate	DMMIAXO	Approved	Betamethasone valerate decreases the expression of Interleukin-2 (IL2).	[17]
Buprenorphine	DMPRI8G	Approved	Buprenorphine decreases the expression of Interleukin-2 (IL2).	[15]
Piperazine	DMTY9LU	Approved	Piperazine decreases the expression of Interleukin-2 (IL2).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Interleukin-2 (IL2).	[21]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine decreases the expression of Interleukin-2 (IL2).	[22]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Interleukin-2 (IL2).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Interleukin-2 (IL2).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-2 (IL2).	[25]
Ribavirin	DMEYLH9	Phase 1 Trial	Ribavirin increases the expression of Interleukin-2 (IL2).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Interleukin-2 (IL2).	[28]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Interleukin-2 (IL2).	[29]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Interleukin-2 (IL2).	[30]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Interleukin-2 (IL2).	[33]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol decreases the expression of Interleukin-2 (IL2).	[35]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid decreases the expression of Interleukin-2 (IL2).	[36]
Icosapentum	DMF1CM7	Investigative	Icosapentum decreases the expression of Interleukin-2 (IL2).	[16]
[3H]CP55940	DMU7FC5	Investigative	[3H]CP55940 decreases the expression of Interleukin-2 (IL2).	[38]
methyl isocyanate	DME4JGF	Investigative	methyl isocyanate increases the expression of Interleukin-2 (IL2).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the secretion of Interleukin-2 (IL2).	[4]
Nicotine	DMWX5CO	Approved	Nicotine decreases the response to substance of Interleukin-2 (IL2).	[8]
Imiquimod	DM1TMA3	Approved	Imiquimod increases the secretion of Interleukin-2 (IL2).	[18]
Naloxone	DM3FXMA	Approved	Naloxone decreases the response to substance of Interleukin-2 (IL2).	[19]
Methylthioadenosine	DMC8J6F	Terminated	Methylthioadenosine decreases the secretion of Interleukin-2 (IL2).	[27]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the secretion of Interleukin-2 (IL2).	[31]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the response to substance of Interleukin-2 (IL2).	[32]
acrolein	DMAMCSR	Investigative	acrolein decreases the secretion of Interleukin-2 (IL2).	[31]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the secretion of Interleukin-2 (IL2).	[34]
Syringic Acid	DM802V7	Investigative	Syringic Acid decreases the secretion of Interleukin-2 (IL2).	[37]
EPZ015666	DM3INX7	Investigative	EPZ015666 decreases the secretion of Interleukin-2 (IL2).	[27]

References

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