Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDYGDJ3)

DOT Name Tumor necrosis factor ligand superfamily member 8 (TNFSF8)
Synonyms CD30 ligand; CD30-L; CD antigen CD153
Gene Name TNFSF8
Related Disease
Acute lymphocytic leukaemia ( )
Adult lymphoma ( )
Advanced cancer ( )
Atopic dermatitis ( )
Autoimmune disease ( )
Bone disease ( )
Burkitt lymphoma ( )
Classic Hodgkin lymphoma ( )
Colitis ( )
Germ cell tumor ( )
Glioma ( )
Helminth infection ( )
Inflammatory bowel disease ( )
Leprosy ( )
Leukemia ( )
Lung cancer ( )
Lung carcinoma ( )
Lymphoma ( )
Mastocytosis ( )
Nasal polyp ( )
Neuralgia ( )
Non-hodgkin lymphoma ( )
Pediatric lymphoma ( )
Plasma cell myeloma ( )
Polyp ( )
Primary biliary cholangitis ( )
Psoriasis ( )
Skin disease ( )
Small lymphocytic lymphoma ( )
Systemic mastocytosis ( )
Tuberculosis ( )
Chronic obstructive pulmonary disease ( )
Crohn disease ( )
Hashimoto thyroiditis ( )
Acute myelogenous leukaemia ( )
Anaplastic large cell lymphoma ( )
UniProt ID
TNFL8_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00229
Sequence
MDPGLQQALNGMAPPGDTAMHVPAGSVASHLGTTSRSYFYLTTATLALCLVFTVATIMVL
VVQRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVAKHLNKTKLSWNKDGI
LHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSVDLKLELLINKHIKKQALVTVCESG
MQTKHVYQNLSQFLLDYLQVNTTISVNVDTFQYIDTSTFPLENVLSIFLYSNSD
Function Cytokine that binds to TNFRSF8/CD30. Induces proliferation of T-cells.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Reactome Pathway
TNFs bind their physiological receptors (R-HSA-5669034 )

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute lymphocytic leukaemia DISPX75S Strong Altered Expression [1]
Adult lymphoma DISK8IZR Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Atopic dermatitis DISTCP41 Strong Biomarker [4]
Autoimmune disease DISORMTM Strong Biomarker [5]
Bone disease DISE1F82 Strong Biomarker [6]
Burkitt lymphoma DIS9D5XU Strong Altered Expression [1]
Classic Hodgkin lymphoma DISV1LU6 Strong Biomarker [5]
Colitis DISAF7DD Strong Biomarker [7]
Germ cell tumor DIS62070 Strong Altered Expression [8]
Glioma DIS5RPEH Strong Biomarker [5]
Helminth infection DIS7CGKY Strong Altered Expression [9]
Inflammatory bowel disease DISGN23E Strong Biomarker [3]
Leprosy DISAA4UI Strong Genetic Variation [10]
Leukemia DISNAKFL Strong Biomarker [11]
Lung cancer DISCM4YA Strong Genetic Variation [12]
Lung carcinoma DISTR26C Strong Genetic Variation [12]
Lymphoma DISN6V4S Strong Biomarker [2]
Mastocytosis DIS1TEE0 Strong Altered Expression [13]
Nasal polyp DISLP3XE Strong Biomarker [14]
Neuralgia DISWO58J Strong Altered Expression [15]
Non-hodgkin lymphoma DISS2Y8A Strong Altered Expression [1]
Pediatric lymphoma DIS51BK2 Strong Biomarker [2]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [6]
Polyp DISRSLYF Strong Altered Expression [14]
Primary biliary cholangitis DIS43E0O Strong Genetic Variation [16]
Psoriasis DIS59VMN Strong Biomarker [17]
Skin disease DISDW8R6 Strong Biomarker [4]
Small lymphocytic lymphoma DIS30POX Strong Altered Expression [18]
Systemic mastocytosis DISNQ2OY Strong Biomarker [13]
Tuberculosis DIS2YIMD Strong Biomarker [19]
Chronic obstructive pulmonary disease DISQCIRF moderate Altered Expression [20]
Crohn disease DIS2C5Q8 moderate Genetic Variation [21]
Hashimoto thyroiditis DIS77CDF moderate Altered Expression [22]
Acute myelogenous leukaemia DISCSPTN Limited Altered Expression [23]
Anaplastic large cell lymphoma DISP4D1R Limited Altered Expression [24]
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⏷ Show the Full List of 36 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 ligand superfamily member 8 (TNFSF8). [25]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [26]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [27]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [28]
Menthol DMG2KW7 Approved Menthol decreases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [29]
Acetic Acid, Glacial DM4SJ5Y Approved Acetic Acid, Glacial increases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [30]
Motexafin gadolinium DMEJKRF Approved Motexafin gadolinium increases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [30]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [9]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [33]
PF-3758309 DM36PKZ Phase 1 PF-3758309 decreases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [34]
Paraquat DMR8O3X Investigative Paraquat decreases the expression of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [35]
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⏷ Show the Full List of 11 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Tumor necrosis factor ligand superfamily member 8 (TNFSF8). [32]
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References

1 Expression and regulation of CD30 ligand and CD30 in human leukemia-lymphoma cell lines.Leukemia. 1994 Dec;8(12):2083-94.
2 Need for an improved molecular/genetic classification for CD30+ lymphomas involving the skin.Cancer Control. 2007 Apr;14(2):124-32. doi: 10.1177/107327480701400205.
3 Therapeutic effects of lentinan on inflammatory bowel disease and colitis-associated cancer.J Cell Mol Med. 2019 Feb;23(2):750-760. doi: 10.1111/jcmm.13897. Epub 2018 Nov 24.
4 Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion.J Clin Invest. 2006 Oct;116(10):2748-56. doi: 10.1172/JCI24274. Epub 2006 Sep 7.
5 CD30 ligand deficiency accelerates glioma progression by promoting the formation of tumor immune microenvironment.Int Immunopharmacol. 2019 Jun;71:350-360. doi: 10.1016/j.intimp.2019.03.055. Epub 2019 Apr 2.
6 Genetic polymorphisms of EPHX1, Gsk3beta, TNFSF8 and myeloma cell DKK-1 expression linked to bone disease in myeloma.Leukemia. 2009 Oct;23(10):1913-9. doi: 10.1038/leu.2009.129. Epub 2009 Aug 6.
7 CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses.J Immunol. 2010 Dec 15;185(12):7671-80. doi: 10.4049/jimmunol.1002229. Epub 2010 Nov 10.
8 Expression of CD30 and CD30 ligand in cultured cell lines from human germ-cell tumors.Lab Invest. 1997 Apr;76(4):497-504.
9 Expression of CD30 mRNA, CD30L mRNA and a variant form of CD30 mRNA in restimulated peripheral blood mononuclear cells (PBMC) of patients with helminthic infections resembling a Th2 disease. Clin Exp Immunol. 1999 Jan;115(1):114-9. doi: 10.1046/j.1365-2249.1999.00774.x.
10 Association of TNFSF8 regulatory variants with excessive inflammatory responses but not leprosy per se.J Infect Dis. 2015 Mar 15;211(6):968-77. doi: 10.1093/infdis/jiu566. Epub 2014 Oct 15.
11 Study of gene expression of CD30 variant (CD30v) and CD30 ligand (CD30L) in acute leukemia.Egypt J Immunol. 2007;14(1):11-20.
12 Association of a novel functional promoter variant (rs2075533 C>T) in the apoptosis gene TNFSF8 with risk of lung cancer--a finding from Texas lung cancer genome-wide association study.Carcinogenesis. 2011 Apr;32(4):507-15. doi: 10.1093/carcin/bgr014. Epub 2011 Feb 2.
13 CD30 in systemic mastocytosis.Immunol Allergy Clin North Am. 2014 May;34(2):341-55. doi: 10.1016/j.iac.2014.01.006. Epub 2014 Mar 13.
14 Increased accumulation of CD30 ligand-positive mast cells associates with eosinophilic inflammation in nasal polyps.Laryngoscope. 2019 Mar;129(3):E110-E117. doi: 10.1002/lary.27658. Epub 2018 Dec 20.
15 Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury.Int J Mol Med. 2019 Oct;44(4):1205-1218. doi: 10.3892/ijmm.2019.4305. Epub 2019 Aug 6.
16 Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.Am J Hum Genet. 2012 Oct 5;91(4):721-8. doi: 10.1016/j.ajhg.2012.08.010. Epub 2012 Sep 20.
17 CD30L/CD30 protects against psoriasiform skin inflammation by suppressing Th17-related cytokine production by V4(+) T cells.J Autoimmun. 2019 Jul;101:70-85. doi: 10.1016/j.jaut.2019.04.009. Epub 2019 Apr 18.
18 Role of the RANKL/RANK system in the induction of interleukin-8 (IL-8) in B chronic lymphocytic leukemia (B-CLL) cells.J Cell Physiol. 2006 Apr;207(1):158-64. doi: 10.1002/jcp.20547.
19 Host resistance to pulmonary Mycobacterium tuberculosis infection requires CD153 expression.Nat Microbiol. 2018 Nov;3(11):1198-1205. doi: 10.1038/s41564-018-0231-6. Epub 2018 Sep 10.
20 CD30 Is Highly Expressed in Chronic Obstructive Pulmonary Disease and Induces the Pulmonary Vascular Remodeling.Biomed Res Int. 2018 Jun 10;2018:3261436. doi: 10.1155/2018/3261436. eCollection 2018.
21 A genome-wide association study identifies 2 susceptibility Loci for Crohn's disease in a Japanese population.Gastroenterology. 2013 Apr;144(4):781-8. doi: 10.1053/j.gastro.2012.12.021. Epub 2012 Dec 22.
22 Immunoexpression of the CD30 ligand/CD30 and IL-6/IL-6R signals in thyroid autoimmune diseases.Histol Histopathol. 2006 Mar;21(3):249-56. doi: 10.14670/HH-21.249.
23 CD30L up-regulates CD30 and IL-4 expression by T cells.FEBS Lett. 2001 Nov 23;508(3):418-22. doi: 10.1016/s0014-5793(01)03076-9.
24 The expression of CD30 in anaplastic large cell lymphoma is regulated by nucleophosmin-anaplastic lymphoma kinase-mediated JunB level in a cell type-specific manner.Cancer Res. 2006 Sep 15;66(18):9002-8. doi: 10.1158/0008-5472.CAN-05-4101.
25 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
26 Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
27 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
28 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
29 Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
30 Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
31 Expression of CD30 mRNA, CD30L mRNA and a variant form of CD30 mRNA in restimulated peripheral blood mononuclear cells (PBMC) of patients with helminthic infections resembling a Th2 disease. Clin Exp Immunol. 1999 Jan;115(1):114-9. doi: 10.1046/j.1365-2249.1999.00774.x.
32 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
33 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
34 Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4. Oncol Rep. 2017 Nov;38(5):2705-2716. doi: 10.3892/or.2017.5989. Epub 2017 Sep 22.
35 Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways. J Toxicol Environ Health A. 2008;71(22):1457-67. doi: 10.1080/15287390802329364.