Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBB2A8O)

• DOT Name: Interleukin-18 (IL18)
• Synonyms: IL-18; Iboctadekin; Interferon gamma-inducing factor; IFN-gamma-inducing factor; Interleukin-1 gamma; IL-1 gamma
• Gene Name: IL18
• UniProt ID: IL18_HUMAN
• PDB ID: 1J0S; 2VXT; 3F62; 3WO2; 3WO3; 3WO4; 4EEE; 4EKX; 4HJJ; 4R6U; 4XFS; 4XFT; 4XFU; 7AL7; 8J6K; 8SPB
• Pfam ID: PF00340
• Sequence:
  MAAEPVEDNCINFVAMKFIDNTLYFIAEDDENLESDYFGKLESKLSVIRNLNDQVLFIDQ
  GNRPLFEDMTDSDCRDNAPRTIFIISMYKDSQPRGMAVTISVKCEKISTLSCENKIISFK
  EMNPPDNIKDTKSDIIFFQRSVPGHDNKMQFESSSYEGYFLACEKERDLFKLILKKEDEL
  GDRSIMFTVQNED
• Function: Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses. Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells. Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore.
• Tissue Specificity: .Expressed in ovarian carcinoma but undetectable in normal ovarian epithelial cells. Resistant to proteolytic activation by caspase-1 and -4.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  NOD-like receptor sig.ling pathway (hsa04621)
  Cytosolic D.-sensing pathway (hsa04623)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Legionellosis (hsa05134)
  Yersinia infection (hsa05135)
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
  Tuberculosis (hsa05152)
  Influenza A (hsa05164)
  Inflammatory bowel disease (hsa05321)
  Rheumatoid arthritis (hsa05323)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Pyroptosis (R-HSA-5620971)
  Interleukin-10 signaling (R-HSA-6783783)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Purinergic signaling in leishmaniasis infection (R-HSA-9660826)
  Interleukin-1 processing (R-HSA-448706)
• BioCyc Pathway: MetaCyc:ENSG00000150782-MONOMER

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
Aspirin	DM672AH	Approved	Interleukin-18 (IL18) affects the response to substance of Aspirin.	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Interleukin-18 (IL18).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-18 (IL18).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-18 (IL18).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interleukin-18 (IL18).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-18 (IL18).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interleukin-18 (IL18).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Interleukin-18 (IL18).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Interleukin-18 (IL18).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Interleukin-18 (IL18).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Interleukin-18 (IL18).	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Interleukin-18 (IL18).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Interleukin-18 (IL18).	[15]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Interleukin-18 (IL18).	[16]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Interleukin-18 (IL18).	[17]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Interleukin-18 (IL18).	[19]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Interleukin-18 (IL18).	[20]
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin increases the expression of Interleukin-18 (IL18).	[21]
Propofol	DMB4OLE	Approved	Propofol increases the expression of Interleukin-18 (IL18).	[22]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Interleukin-18 (IL18).	[22]
Gentamicin	DMKINJO	Approved	Gentamicin decreases the expression of Interleukin-18 (IL18).	[23]
Cimetidine	DMH61ZB	Approved	Cimetidine increases the expression of Interleukin-18 (IL18).	[24]
Ergotidine	DM78IME	Approved	Ergotidine increases the expression of Interleukin-18 (IL18).	[24]
Ropivacaine	DMSPJG2	Approved	Ropivacaine increases the expression of Interleukin-18 (IL18).	[25]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Interleukin-18 (IL18).	[26]
Benzylpenicillin	DMS9503	Phase 3	Benzylpenicillin increases the expression of Interleukin-18 (IL18).	[27]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Interleukin-18 (IL18).	[27]
LY294002	DMY1AFS	Phase 1	LY294002 increases the expression of Interleukin-18 (IL18).	[29]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Interleukin-18 (IL18).	[27]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Interleukin-18 (IL18).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interleukin-18 (IL18).	[32]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Interleukin-18 (IL18).	[33]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Interleukin-18 (IL18).	[34]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Interleukin-18 (IL18).	[35]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Interleukin-18 (IL18).	[36]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Interleukin-18 (IL18).	[9]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Interleukin-18 (IL18).	[37]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Interleukin-18 (IL18).	[38]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Interleukin-18 (IL18).	[37]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Interleukin-18 (IL18).	[39]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Interleukin-18 (IL18).	[41]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Interleukin-18 (IL18).	[42]
NSC-1771	DMNXDGQ	Investigative	NSC-1771 increases the expression of Interleukin-18 (IL18).	[27]
Lysophosphatidylcholine	DMOGFVH	Investigative	Lysophosphatidylcholine increases the expression of Interleukin-18 (IL18).	[44]
citral	DM53ZGY	Investigative	citral increases the expression of Interleukin-18 (IL18).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the secretion of Interleukin-18 (IL18).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the secretion of Interleukin-18 (IL18).	[14]
Nicotine	DMWX5CO	Approved	Nicotine increases the secretion of Interleukin-18 (IL18).	[18]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the response to substance of Interleukin-18 (IL18).	[40]
Protoporphyrin IX	DMWYE7A	Investigative	Protoporphyrin IX decreases the response to substance of Interleukin-18 (IL18).	[40]
BAY11-7082	DMQNOFA	Investigative	BAY11-7082 decreases the secretion of Interleukin-18 (IL18).	[43]
Biliverdine Ix Alpha	DMCA0WJ	Investigative	Biliverdine Ix Alpha decreases the response to substance of Interleukin-18 (IL18).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid increases the methylation of Interleukin-18 (IL18).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Interleukin-18 (IL18).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interleukin-18 (IL18).	[31]
Choline	DM5D9YK	Investigative	Choline increases the methylation of Interleukin-18 (IL18).	[12]

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