Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS7T5VH)

• DOT Name: Interleukin-8 (CXCL8)
• Synonyms: IL-8; C-X-C motif chemokine 8; Chemokine (C-X-C motif) ligand 8; Emoctakin; Granulocyte chemotactic protein 1; GCP-1; Monocyte-derived neutrophil chemotactic factor; MDNCF; Monocyte-derived neutrophil-activating peptide; MONAP; Neutrophil-activating protein 1; NAP-1; Protein 3-10C; T-cell chemotactic factor
• Gene Name: CXCL8
• UniProt ID: IL8_HUMAN
• PDB ID: 1ICW; 1IKL; 1IKM; 1IL8; 1ILP; 1ILQ; 1QE6; 1ROD; 2IL8; 3IL8; 4XDX; 5D14; 5WDZ; 6LFM; 6LFO; 6N2U; 6WZM; 6XMN; 8IC0
• Pfam ID: PF00048
• Sequence:
  MTSKLAVALLAAFLISAALCEGAVLPRSAKELRCQCIKTYSKPFHPKFIKELRVIESGPH
  CANTEIIVKLSDGRELCLDPKENWVQRVVEKFLKRAENS
• Function: Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection. Also plays an important role in neutrophil activation. Released in response to an inflammatory stimulus, exerts its effect by binding to the G-protein-coupled receptors CXCR1 and CXCR2, primarily found in neutrophils, monocytes and endothelial cells. G-protein heterotrimer (alpha, beta, gamma subunits) constitutively binds to CXCR1/CXCR2 receptor and activation by IL8 leads to beta and gamma subunits release from Galpha (GNAI2 in neutrophils) and activation of several downstream signaling pathways including PI3K and MAPK pathways.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  NF-kappa B sig.ling pathway (hsa04064)
  Phospholipase D sig.ling pathway (hsa04072)
  Cellular senescence (hsa04218)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  IL-17 sig.ling pathway (hsa04657)
  Non-alcoholic fatty liver disease (hsa04932)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Alcoholic liver disease (hsa04936)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Yersinia infection (hsa05135)
  Chagas disease (hsa05142)
  Malaria (hsa05144)
  Amoebiasis (hsa05146)
  Hepatitis B (hsa05161)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Bladder cancer (hsa05219)
  Rheumatoid arthritis (hsa05323)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Peptide ligand-binding receptors (R-HSA-375276)
  Chemokine receptors bind chemokines (R-HSA-380108)
  ATF4 activates genes in response to endoplasmic reticulum stress (R-HSA-380994)
  G alpha (i) signalling events (R-HSA-418594)
  Interleukin-10 signaling (R-HSA-6783783)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)

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
Epinephrine	DM3KJBC	Approved	Interleukin-8 (CXCL8) increases the Inflammation ADR of Epinephrine.	[87]
Rituximab	DM1YVZT	Approved	Interleukin-8 (CXCL8) increases the Adverse drug reaction ADR of Rituximab.	[87]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Interleukin-8 (CXCL8).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-8 (CXCL8).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-8 (CXCL8).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-8 (CXCL8).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interleukin-8 (CXCL8).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interleukin-8 (CXCL8).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Interleukin-8 (CXCL8).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interleukin-8 (CXCL8).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Interleukin-8 (CXCL8).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Interleukin-8 (CXCL8).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Interleukin-8 (CXCL8).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interleukin-8 (CXCL8).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Interleukin-8 (CXCL8).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Interleukin-8 (CXCL8).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interleukin-8 (CXCL8).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Interleukin-8 (CXCL8).	[16]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Interleukin-8 (CXCL8).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Interleukin-8 (CXCL8).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Interleukin-8 (CXCL8).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interleukin-8 (CXCL8).	[20]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Interleukin-8 (CXCL8).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Interleukin-8 (CXCL8).	[23]
Selenium	DM25CGV	Approved	Selenium increases the expression of Interleukin-8 (CXCL8).	[24]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Interleukin-8 (CXCL8).	[25]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Interleukin-8 (CXCL8).	[26]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Interleukin-8 (CXCL8).	[27]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Interleukin-8 (CXCL8).	[28]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Interleukin-8 (CXCL8).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-8 (CXCL8).	[29]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Interleukin-8 (CXCL8).	[30]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Interleukin-8 (CXCL8).	[31]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Interleukin-8 (CXCL8).	[32]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Interleukin-8 (CXCL8).	[33]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Interleukin-8 (CXCL8).	[34]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Interleukin-8 (CXCL8).	[36]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interleukin-8 (CXCL8).	[37]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Interleukin-8 (CXCL8).	[39]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Interleukin-8 (CXCL8).	[40]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Interleukin-8 (CXCL8).	[41]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Interleukin-8 (CXCL8).	[42]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Interleukin-8 (CXCL8).	[43]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Interleukin-8 (CXCL8).	[44]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Interleukin-8 (CXCL8).	[37]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Interleukin-8 (CXCL8).	[45]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the activity of Interleukin-8 (CXCL8).	[46]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Interleukin-8 (CXCL8).	[48]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Interleukin-8 (CXCL8).	[49]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Interleukin-8 (CXCL8).	[51]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the expression of Interleukin-8 (CXCL8).	[52]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Interleukin-8 (CXCL8).	[54]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Interleukin-8 (CXCL8).	[55]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Interleukin-8 (CXCL8).	[56]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Interleukin-8 (CXCL8).	[58]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Interleukin-8 (CXCL8).	[59]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Interleukin-8 (CXCL8).	[1]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Interleukin-8 (CXCL8).	[60]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Interleukin-8 (CXCL8).	[61]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Interleukin-8 (CXCL8).	[62]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the activity of Interleukin-8 (CXCL8).	[63]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Interleukin-8 (CXCL8).	[1]
Colchicine	DM2POTE	Approved	Colchicine increases the expression of Interleukin-8 (CXCL8).	[56]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interleukin-8 (CXCL8).	[64]
Vitamin C	DMXJ7O8	Approved	Vitamin C affects the expression of Interleukin-8 (CXCL8).	[65]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Interleukin-8 (CXCL8).	[67]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Interleukin-8 (CXCL8).	[68]
Imatinib	DM7RJXL	Approved	Imatinib increases the expression of Interleukin-8 (CXCL8).	[69]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Interleukin-8 (CXCL8).	[70]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Interleukin-8 (CXCL8).	[1]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Interleukin-8 (CXCL8).	[37]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Interleukin-8 (CXCL8).	[56]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Interleukin-8 (CXCL8).	[72]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the expression of Interleukin-8 (CXCL8).	[73]
Bosentan	DMIOGBU	Approved	Bosentan increases the expression of Interleukin-8 (CXCL8).	[74]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Interleukin-8 (CXCL8).	[1]
Glutathione	DMAHMT9	Approved	Glutathione decreases the expression of Interleukin-8 (CXCL8).	[76]
Ximelegatran	DMU8ANS	Approved	Ximelegatran increases the expression of Interleukin-8 (CXCL8).	[77]
Bleomycin	DMNER5S	Approved	Bleomycin increases the expression of Interleukin-8 (CXCL8).	[78]
Methimazole	DM25FL8	Approved	Methimazole increases the expression of Interleukin-8 (CXCL8).	[80]
Mebendazole	DMO14SG	Approved	Mebendazole increases the expression of Interleukin-8 (CXCL8).	[81]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Interleukin-8 (CXCL8).	[1]
Clotrimazole	DMMFCIH	Approved	Clotrimazole increases the expression of Interleukin-8 (CXCL8).	[82]
Clavulanate	DM2FGRT	Approved	Clavulanate decreases the expression of Interleukin-8 (CXCL8).	[1]
Ergotidine	DM78IME	Approved	Ergotidine increases the expression of Interleukin-8 (CXCL8).	[83]
Benzoic acid	DMKB9FI	Approved	Benzoic acid increases the expression of Interleukin-8 (CXCL8).	[84]
Sulfasalazine	DMICA9H	Approved	Sulfasalazine decreases the expression of Interleukin-8 (CXCL8).	[85]
Flutamide	DMK0O7U	Approved	Flutamide increases the expression of Interleukin-8 (CXCL8).	[1]
Sodium chloride	DMM3950	Approved	Sodium chloride increases the expression of Interleukin-8 (CXCL8).	[86]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol decreases the methylation of Interleukin-8 (CXCL8).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the secretion of Interleukin-8 (CXCL8).	[35]
Ethanol	DMDRQZU	Approved	Ethanol increases the secretion of Interleukin-8 (CXCL8).	[38]
Clozapine	DMFC71L	Approved	Clozapine decreases the secretion of Interleukin-8 (CXCL8).	[47]
Menthol	DMG2KW7	Approved	Menthol increases the secretion of Interleukin-8 (CXCL8).	[50]
Cocaine	DMSOX7I	Approved	Cocaine increases the secretion of Interleukin-8 (CXCL8).	[53]
Vinblastine	DM5TVS3	Approved	Vinblastine increases the stability of Interleukin-8 (CXCL8).	[57]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone decreases the secretion of Interleukin-8 (CXCL8).	[66]
Ritonavir	DMU764S	Approved	Ritonavir increases the secretion of Interleukin-8 (CXCL8).	[71]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the secretion of Interleukin-8 (CXCL8).	[68]
Capecitabine	DMTS85L	Approved	Capecitabine increases the secretion of Interleukin-8 (CXCL8).	[28]
Ardeparin	DMYRX8B	Approved	Ardeparin increases the secretion of Interleukin-8 (CXCL8).	[75]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR decreases the secretion of Interleukin-8 (CXCL8).	[79]

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