Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1G9297)

• DOT Name: Tumor necrosis factor alpha-induced protein 8 (TNFAIP8)
• Synonyms: TNF alpha-induced protein 8; Head and neck tumor and metastasis-related protein; MDC-3.13; NF-kappa-B-inducible DED-containing protein; NDED; SCC-S2; TNF-induced protein GG2-1
• Gene Name: TNFAIP8
• Related Disease:
  Acute graft versus host disease
  Asthma
  Autoimmune disease
  B-cell neoplasm
  Cervical cancer
  Cervical carcinoma
  Colitis
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Diabetic kidney disease
  Dilated cardiomyopathy 1A
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Head-neck squamous cell carcinoma
  Invasive ductal breast carcinoma
  Juvenile idiopathic arthritis
  Liver failure
  Lung cancer
  Lung carcinoma
  Lymphoma, non-Hodgkin, familial
  Neoplasm
  Non-hodgkin lymphoma
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Gastric cancer
  Hepatocellular carcinoma
  Stomach cancer
  Adenocarcinoma
  Pachyonychia congenita 3
  Bone osteosarcoma
  Breast cancer
  Immune system disorder
  Melanoma
  Non-small-cell lung cancer
  Osteosarcoma
• UniProt ID: TFIP8_HUMAN
• Pfam ID: PF05527
• Sequence:
  MHSEAEESKEVATDVFNSKNLAVQAQKKILGKMVSKSIATTLIDDTSSEVLDELYRVTRE
  YTQNKKEAEKIIKNLIKTVIKLAILYRNNQFNQDELALMEKFKKKVHQLAMTVVSFHQVD
  YTFDRNVLSRLLNECREMLHQIIQRHLTAKSHGRVNNVFDHFSDCEFLAALYNPFGNFKP
  HLQKLCDGINKMLDEENI
• Function: Acts as a negative mediator of apoptosis and may play a role in tumor progression. Suppresses the TNF-mediated apoptosis by inhibiting caspase-8 activity but not the processing of procaspase-8, subsequently resulting in inhibition of BID cleavage and caspase-3 activation.
• Tissue Specificity: Expressed at high levels in the spleen, lymph node, thymus, thyroid, bone marrow and placenta. Expressed at high levels both in various tumor tissues, unstimulated and cytokine-activated cultured cells. Expressed at low levels in the spinal cord, ovary, lung, adrenal glands, heart, brain, testis and skeletal muscle.
• Reactome Pathway: PI Metabolism (R-HSA-1483255)

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute graft versus host disease	DIS8KLVM	Strong	Biomarker	[1]
Asthma	DISW9QNS	Strong	Genetic Variation	[2]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[3]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[4]
Cervical cancer	DISFSHPF	Strong	Biomarker	[4]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[4]
Colitis	DISAF7DD	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[8]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[9]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[10]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[13]
Invasive ductal breast carcinoma	DIS43J58	Strong	Biomarker	[9]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[14]
Liver failure	DISLGEL6	Strong	Altered Expression	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[16]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[18]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[11]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[11]
Prostate cancer	DISF190Y	Strong	Altered Expression	[19]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[19]
Prostate neoplasm	DISHDKGQ	Strong	Posttranslational Modification	[20]
Gastric cancer	DISXGOUK	moderate	Biomarker	[21]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[22]
Stomach cancer	DISKIJSX	moderate	Biomarker	[21]
Adenocarcinoma	DIS3IHTY	Disputed	Altered Expression	[23]
Pachyonychia congenita 3	DISZLC6C	Disputed	Altered Expression	[23]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[24]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[25]
Immune system disorder	DISAEGPH	Limited	Altered Expression	[26]
Melanoma	DIS1RRCY	Limited	Altered Expression	[25]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[27]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[24]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) affects the response to substance of Topotecan.	[50]

25 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 Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[28]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[30]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[31]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[33]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[35]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[36]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[37]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[38]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[39]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[40]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[41]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[31]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[31]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[31]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[42]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[42]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[43]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[44]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[46]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[48]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tumor necrosis factor alpha-induced protein 8 (TNFAIP8).	[47]

References

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