Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0DWXXB)

• DOT Name: Interleukin-1 beta (IL1B)
• Synonyms: IL-1 beta; Catabolin
• Gene Name: IL1B
• Related Disease: Hereditary diffuse gastric adenocarcinoma
• UniProt ID: IL1B_HUMAN
• PDB ID: 1HIB ; 1I1B ; 1IOB ; 1ITB ; 1L2H ; 1S0L ; 1T4Q ; 1TOO ; 1TP0 ; 1TWE ; 1TWM ; 21BI ; 2I1B ; 2KH2 ; 2NVH ; 31BI ; 3LTQ ; 3O4O ; 3POK ; 41BI ; 4DEP ; 4G6J ; 4G6M ; 4GAF ; 4GAI ; 4I1B ; 5BVP ; 5I1B ; 5MVZ ; 5R7W ; 5R85 ; 5R86 ; 5R87 ; 5R88 ; 5R89 ; 5R8A ; 5R8B ; 5R8C ; 5R8D ; 5R8E ; 5R8F ; 5R8G ; 5R8H ; 5R8I ; 5R8J ; 5R8K ; 5R8L ; 5R8M ; 5R8N ; 5R8O ; 5R8P ; 5R8Q ; 6I1B ; 6Y8I ; 6Y8M ; 7CHY ; 7CHZ ; 7I1B ; 7Z4T ; 8C3U ; 9ILB
• Pfam ID: PF00340 ; PF02394
• Sequence:
  MAEVPELASEMMAYYSGNEDDLFFEADGPKQMKCSFQDLDLCPLDGGIQLRISDHHYSKG
  FRQAASVVVAMDKLRKMLVPCPQTFQENDLSTFFPFIFEEEPIFFDTWDNEAYVHDAPVR
  SLNCTLRDSQQKSLVMSGPYELKALHLQGQDMEQQVVFSMSFVQGEESNDKIPVALGLKE
  KNLYLSCVLKDDKPTLQLESVDPKNYPKKKMEKRFVFNKIEINNKLEFESAQFPNWYIST
  SQAENMPVFLGGTKGGQDITDFTMQFVSS
• Function: Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells. Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6. 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. Acts as a sensor of S.pyogenes infection in skin: cleaved and activated by pyogenes SpeB protease, leading to an inflammatory response that prevents bacterial growth during invasive skin infection.
• Tissue Specificity: Expressed in activated monocytes/macrophages (at protein level).
• KEGG Pathway:
  Antifolate resistance (hsa01523)
  MAPK sig.ling pathway (hsa04010)
  Cytokine-cytokine receptor interaction (hsa04060)
  NF-kappa B sig.ling pathway (hsa04064)
  Necroptosis (hsa04217)
  Osteoclast differentiation (hsa04380)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  Cytosolic D.-sensing pathway (hsa04623)
  C-type lectin receptor sig.ling pathway (hsa04625)
  Hematopoietic cell lineage (hsa04640)
  IL-17 sig.ling pathway (hsa04657)
  Th17 cell differentiation (hsa04659)
  TNF sig.ling pathway (hsa04668)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Non-alcoholic fatty liver disease (hsa04932)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Alcoholic liver disease (hsa04936)
  Type I diabetes mellitus (hsa04940)
  Alzheimer disease (hsa05010)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Yersinia infection (hsa05135)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Herpes simplex virus 1 infection (hsa05168)
  Coro.virus disease - COVID-19 (hsa05171)
  Inflammatory bowel disease (hsa05321)
  Rheumatoid arthritis (hsa05323)
  Graft-versus-host disease (hsa05332)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Pyroptosis (R-HSA-5620971)
  CLEC7A/inflammasome pathway (R-HSA-5660668)
  Interleukin-10 signaling (R-HSA-6783783)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Interleukin-1 signaling (R-HSA-9020702)
  Purinergic signaling in leishmaniasis infection (R-HSA-9660826)
  Interleukin-1 processing (R-HSA-448706)
• BioCyc Pathway: MetaCyc:ENSG00000125538-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	No Known	Unknown	[1]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Interleukin-1 beta (IL1B) affects the response to substance of Mitomycin.	[70]
Vinblastine	DM5TVS3	Approved	Interleukin-1 beta (IL1B) affects the response to substance of Vinblastine.	[70]
Capsaicin	DMGMF6V	Approved	Interleukin-1 beta (IL1B) increases the response to substance of Capsaicin.	[71]
Midazolam	DMXOELT	Approved	Interleukin-1 beta (IL1B) increases the Cytokine release syndrome ADR of Midazolam.	[74]
Uracil mustard	DMHL7OB	Approved	Interleukin-1 beta (IL1B) increases the Skin and subcutaneous tissue disorders ADR of Uracil mustard.	[74]
Camptothecin	DM6CHNJ	Phase 3	Interleukin-1 beta (IL1B) decreases the response to substance of Camptothecin.	[75]

This DOT Affected the Regulation of Drug Effects of 9 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitric Oxide	DM1RBYG	Approved	Interleukin-1 beta (IL1B) increases the abundance of Nitric Oxide.	[72]
Dehydroepiandrosterone sulfate	DM4Q80H	Approved	Interleukin-1 beta (IL1B) increases the abundance of Dehydroepiandrosterone sulfate.	[73]
LTB4	DME26RS	Phase 2	Interleukin-1 beta (IL1B) increases the abundance of LTB4.	[76]
Taurocholic acid	DM2LZ8F	Phase 1/2	Interleukin-1 beta (IL1B) decreases the import of Taurocholic acid.	[77]
PGF2alpha	DM4XAU7	Clinical trial	Interleukin-1 beta (IL1B) increases the abundance of PGF2alpha.	[73]
[3H]cAMP	DMZRQU7	Investigative	Interleukin-1 beta (IL1B) increases the abundance of [3H]cAMP.	[78]
PGD2	DMYDW6J	Investigative	Interleukin-1 beta (IL1B) increases the abundance of PGD2.	[79]
Nitrate	DMVFB93	Investigative	Interleukin-1 beta (IL1B) increases the abundance of Nitrate.	[80]
Nitrite	DMR5XT3	Investigative	Interleukin-1 beta (IL1B) increases the abundance of Nitrite.	[80]

86 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-1 beta (IL1B).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Interleukin-1 beta (IL1B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-1 beta (IL1B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interleukin-1 beta (IL1B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interleukin-1 beta (IL1B).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-1 beta (IL1B).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interleukin-1 beta (IL1B).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Interleukin-1 beta (IL1B).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Interleukin-1 beta (IL1B).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Interleukin-1 beta (IL1B).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Interleukin-1 beta (IL1B).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interleukin-1 beta (IL1B).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Interleukin-1 beta (IL1B).	[15]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Interleukin-1 beta (IL1B).	[16]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Interleukin-1 beta (IL1B).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Interleukin-1 beta (IL1B).	[18]
Selenium	DM25CGV	Approved	Selenium increases the expression of Interleukin-1 beta (IL1B).	[19]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Interleukin-1 beta (IL1B).	[20]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Interleukin-1 beta (IL1B).	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Interleukin-1 beta (IL1B).	[21]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Interleukin-1 beta (IL1B).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-1 beta (IL1B).	[22]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Interleukin-1 beta (IL1B).	[24]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Interleukin-1 beta (IL1B).	[25]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Interleukin-1 beta (IL1B).	[26]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Interleukin-1 beta (IL1B).	[27]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Interleukin-1 beta (IL1B).	[29]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Interleukin-1 beta (IL1B).	[30]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Interleukin-1 beta (IL1B).	[31]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Interleukin-1 beta (IL1B).	[32]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Interleukin-1 beta (IL1B).	[33]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Interleukin-1 beta (IL1B).	[34]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Interleukin-1 beta (IL1B).	[36]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Interleukin-1 beta (IL1B).	[37]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Interleukin-1 beta (IL1B).	[38]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Interleukin-1 beta (IL1B).	[29]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Interleukin-1 beta (IL1B).	[39]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Interleukin-1 beta (IL1B).	[41]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Interleukin-1 beta (IL1B).	[42]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Interleukin-1 beta (IL1B).	[43]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Interleukin-1 beta (IL1B).	[44]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Interleukin-1 beta (IL1B).	[4]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Interleukin-1 beta (IL1B).	[2]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Interleukin-1 beta (IL1B).	[45]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Interleukin-1 beta (IL1B).	[46]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Interleukin-1 beta (IL1B).	[2]
Colchicine	DM2POTE	Approved	Colchicine increases the expression of Interleukin-1 beta (IL1B).	[29]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interleukin-1 beta (IL1B).	[16]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone decreases the expression of Interleukin-1 beta (IL1B).	[29]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of Interleukin-1 beta (IL1B).	[48]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the expression of Interleukin-1 beta (IL1B).	[2]
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin increases the expression of Interleukin-1 beta (IL1B).	[50]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the expression of Interleukin-1 beta (IL1B).	[51]
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the expression of Interleukin-1 beta (IL1B).	[2]
Propofol	DMB4OLE	Approved	Propofol decreases the expression of Interleukin-1 beta (IL1B).	[52]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the expression of Interleukin-1 beta (IL1B).	[2]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Interleukin-1 beta (IL1B).	[52]
Warfarin	DMJYCVW	Approved	Warfarin decreases the expression of Interleukin-1 beta (IL1B).	[29]
Glutathione	DMAHMT9	Approved	Glutathione decreases the expression of Interleukin-1 beta (IL1B).	[54]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid decreases the expression of Interleukin-1 beta (IL1B).	[55]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus increases the expression of Interleukin-1 beta (IL1B).	[29]
Bleomycin	DMNER5S	Approved	Bleomycin increases the expression of Interleukin-1 beta (IL1B).	[57]
Mebendazole	DMO14SG	Approved	Mebendazole increases the expression of Interleukin-1 beta (IL1B).	[2]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Interleukin-1 beta (IL1B).	[2]
Nifedipine	DMSVOZT	Approved	Nifedipine increases the expression of Interleukin-1 beta (IL1B).	[58]
Clavulanate	DM2FGRT	Approved	Clavulanate increases the expression of Interleukin-1 beta (IL1B).	[2]
Sulfasalazine	DMICA9H	Approved	Sulfasalazine decreases the expression of Interleukin-1 beta (IL1B).	[59]
Flutamide	DMK0O7U	Approved	Flutamide increases the expression of Interleukin-1 beta (IL1B).	[58]
Sodium chloride	DMM3950	Approved	Sodium chloride increases the expression of Interleukin-1 beta (IL1B).	[36]
Nelfinavir mesylate	DMFX6G8	Approved	Nelfinavir mesylate increases the expression of Interleukin-1 beta (IL1B).	[60]
Flurbiprofen	DMGN4BY	Approved	Flurbiprofen increases the expression of Interleukin-1 beta (IL1B).	[51]
Nicotinamide	DMUPE07	Approved	Nicotinamide decreases the expression of Interleukin-1 beta (IL1B).	[29]
Etodolac	DM6WJO9	Approved	Etodolac increases the expression of Interleukin-1 beta (IL1B).	[2]
Pentamidine	DMHZJCG	Approved	Pentamidine decreases the expression of Interleukin-1 beta (IL1B).	[29]
Ropivacaine	DMSPJG2	Approved	Ropivacaine increases the expression of Interleukin-1 beta (IL1B).	[65]
Salbutamol	DMN9CWF	Approved	Salbutamol decreases the expression of Interleukin-1 beta (IL1B).	[2]
Salicyclic acid	DM2F8XZ	Approved	Salicyclic acid increases the expression of Interleukin-1 beta (IL1B).	[66]
Spironolactone	DM2AQ5N	Approved	Spironolactone increases the expression of Interleukin-1 beta (IL1B).	[67]
Dobutamine	DMD1B8Z	Approved	Dobutamine decreases the expression of Interleukin-1 beta (IL1B).	[2]
Zafirlukast	DMHNQOG	Approved	Zafirlukast decreases the expression of Interleukin-1 beta (IL1B).	[2]
Stavudine	DM6DEK9	Approved	Stavudine increases the expression of Interleukin-1 beta (IL1B).	[60]
Fexofenadine	DM17ONX	Approved	Fexofenadine decreases the expression of Interleukin-1 beta (IL1B).	[2]
Imiquimod	DM1TMA3	Approved	Imiquimod increases the expression of Interleukin-1 beta (IL1B).	[68]
Entacapone	DMLBVKQ	Approved	Entacapone increases the expression of Interleukin-1 beta (IL1B).	[2]
Paroxetine	DM5PVQE	Approved	Paroxetine affects the expression of Interleukin-1 beta (IL1B).	[69]
Trazodone	DMK1GBJ	Approved	Trazodone increases the expression of Interleukin-1 beta (IL1B).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the response to substance of Interleukin-1 beta (IL1B).	[14]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the secretion of Interleukin-1 beta (IL1B).	[28]
Nicotine	DMWX5CO	Approved	Nicotine increases the secretion of Interleukin-1 beta (IL1B).	[35]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the secretion of Interleukin-1 beta (IL1B).	[40]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the secretion of Interleukin-1 beta (IL1B).	[47]
Imatinib	DM7RJXL	Approved	Imatinib increases the secretion of Interleukin-1 beta (IL1B).	[49]
Melatonin	DMKWFBT	Approved	Melatonin decreases the secretion of Interleukin-1 beta (IL1B).	[53]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the response to substance of Interleukin-1 beta (IL1B).	[56]
Masoprocol	DMMVNZ0	Approved	Masoprocol decreases the response to substance of Interleukin-1 beta (IL1B).	[56]
Mefenamic acid	DMK7HFI	Approved	Mefenamic acid decreases the secretion of Interleukin-1 beta (IL1B).	[61]
Ketamine	DMT5HA4	Approved	Ketamine increases the secretion of Interleukin-1 beta (IL1B).	[62]
Budesonide	DMJIBAW	Approved	Budesonide decreases the secretion of Interleukin-1 beta (IL1B).	[63]
Flucloxacillin	DMNUWST	Approved	Flucloxacillin increases the secretion of Interleukin-1 beta (IL1B).	[64]

1 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-1 beta (IL1B).	[23]

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