Details of Drug Off-Target (DOT)

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

• DOT Name: Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1)
• Synonyms: TIPE1; TNF alpha-induced protein 8-like protein 1; TNFAIP8-like protein 1; Oxidative stress-regulated gene-beta; Oxy-beta
• Gene Name: TNFAIP8L1
• Related Disease:
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Hepatocellular carcinoma
  Osteosarcoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Stomach cancer
• UniProt ID: TP8L1_HUMAN
• Pfam ID: PF05527
• Sequence:
  MDTFSTKSLALQAQKKLLSKMASKAVVAVLVDDTSSEVLDELYRATREFTRSRKEAQKML
  KNLVKVALKLGLLLRGDQLGGEELALLRRFRHRARCLAMTAVSFHQVDFTFDRRVLAAGL
  LECRDLLHQAVGPHLTAKSHGRINHVFGHLADCDFLAALYGPAEPYRSHLRRICEGLGRM
  LDEGSL
• Function: Acts as a negative regulator of mTOR activity.
• Tissue Specificity: High expression detected in most carcinoma cell lines, especially in cells transformed with virus genomes.
• Reactome Pathway: PI Metabolism (R-HSA-1483255)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	moderate	Biomarker	[8]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[8]
Gastric cancer	DISXGOUK	Limited	Biomarker	[9]
Lung cancer	DISCM4YA	Limited	Biomarker	[10]
Lung carcinoma	DISTR26C	Limited	Biomarker	[10]
Lung neoplasm	DISVARNB	Limited	Altered Expression	[10]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]
Stomach cancer	DISKIJSX	Limited	Biomarker	[9]

12 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 Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[20]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[21]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 1 (TNFAIP8L1).	[22]

References

• [1] TIPE1 Inhibits Breast Cancer Proliferation by Downregulating ERK Phosphorylation and Predicts a Favorable Prognosis.Front Oncol. 2019 May 22;9:400. doi: 10.3389/fonc.2019.00400. eCollection 2019.
• [2] TIPE1 accelerates atherogenesis by inducing endothelial dysfunction in response to oxidative stress.Biochim Biophys Acta Mol Basis Dis. 2020 Jan 1;1866(1):165578. doi: 10.1016/j.bbadis.2019.165578. Epub 2019 Oct 28.
• [3] Transcriptome Analysis of Peripheral Blood in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients Identifies TNFR1 and TLR Pathways in the IVIg Response.Medicine (Baltimore). 2016 May;95(19):e3370. doi: 10.1097/MD.0000000000003370.
• [4] TIPE1 suppresses osteosarcoma tumor growth by regulating macrophage infiltration.Clin Transl Oncol. 2019 Mar;21(3):334-341. doi: 10.1007/s12094-018-1927-z. Epub 2018 Jul 30.
• [5] TIPE1 suppresses the invasion and migration of breast cancer cells and inhibits epithelial-to-mesenchymal transition primarily via the ERK signaling pathway.Acta Biochim Biophys Sin (Shanghai). 2019 Sep 6;51(10):1008-1015. doi: 10.1093/abbs/gmz099.
• [6] TIPE1 promotes cervical cancer progression by repression of p53 acetylation and is associated with poor cervical cancer outcome.Carcinogenesis. 2019 Jun 10;40(4):592-599. doi: 10.1093/carcin/bgy163.
• [7] TIPE1 induces apoptosis by negatively regulating Rac1 activation in hepatocellular carcinoma cells.Oncogene. 2015 May 14;34(20):2566-74. doi: 10.1038/onc.2014.208. Epub 2014 Jul 21.
• [8] TIPE1 impairs stemness maintenance in colorectal cancer through directly targeting -catenin.Carcinogenesis. 2020 Mar 13;41(1):25-35. doi: 10.1093/carcin/bgz079.
• [9] TIPE1 suppresses invasion and migration through down-regulating Wnt/-catenin pathway in gastric cancer.J Cell Mol Med. 2018 Feb;22(2):1103-1117. doi: 10.1111/jcmm.13362. Epub 2017 Oct 10.
• [10] TIPE1 function as a prognosis predictor and negative regulator of lung cancer.Oncotarget. 2017 Jul 28;8(45):78496-78506. doi: 10.18632/oncotarget.19655. eCollection 2017 Oct 3.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [13] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [17] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [21] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [22] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.