Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT90OWIO)

• DOT Name: Tumor necrosis factor ligand superfamily member 13 (TNFSF13)
• Synonyms: A proliferation-inducing ligand; APRIL; TNF- and APOL-related leukocyte expressed ligand 2; TALL-2; TNF-related death ligand 1; TRDL-1; CD antigen CD256
• Gene Name: TNFSF13
• Related Disease: Common variable immunodeficiency
• UniProt ID: TNF13_HUMAN
• PDB ID: 4ZCH
• Pfam ID: PF00229
• Sequence:
  MPASSPFLLAPKGPPGNMGGPVREPALSVALWLSWGAALGAVACAMALLTQQTELQSLRR
  EVSRLQGTGGPSQNGEGYPWQSLPEQSSDALEAWENGERSRKRRAVLTQKQKKQHSVLHL
  VPINATSKDDSDVTEVMWQPALRRGRGLQAQGYGVRIQDAGVYLLYSQVLFQDVTFTMGQ
  VVSREGQGRQETLFRCIRSMPSHPDRAYNSCYSAGVFHLHQGDILSVIIPRARAKLNLSP
  HGTFLGFVKL
• Function: Cytokine that binds to TNFRSF13B/TACI and to TNFRSF17/BCMA. Plays a role in the regulation of tumor cell growth. May be involved in monocyte/macrophage-mediated immunological processes.
• Tissue Specificity: Expressed at high levels in transformed cell lines, cancers of colon, thyroid, lymphoid tissues and specifically expressed in monocytes and macrophages.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Intesti.l immune network for IgA production (hsa04672)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  TNFs bind their physiological receptors (R-HSA-5669034)
  HuR (ELAVL1) binds and stabilizes mRNA (R-HSA-450520)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Common variable immunodeficiency	DISHE7JQ	Limited	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[6]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[3]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[7]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[8]
Cetrorelix	DMFD9Q6	Approved	Cetrorelix decreases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tumor necrosis factor ligand superfamily member 13 (TNFSF13).	[10]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [3] [Expression of APRIL in colorectal carcinoma tissues and effects of chemotherapeutic agents on APRIL expression in colorectal carcinoma SW480 cells]. Ai Zheng. 2008 Apr;27(4):369-73.
• [4] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
• [7] Marked regression of liver metastasis by combined therapy of ultrasound-mediated NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse. Int J Cancer. 2008 Apr 1;122(7):1645-56. doi: 10.1002/ijc.23280.
• [8] 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.
• [9] Luteinizing Hormone-Releasing Hormone (LHRH)-I antagonist cetrorelix inhibits myeloma cell growth in vitro and in vivo. Mol Cancer Ther. 2011 Jan;10(1):148-58. doi: 10.1158/1535-7163.MCT-10-0829. Epub 2010 Nov 9.
• [10] Chlorophyllin significantly reduces benzo[a]pyrene-DNA adduct formation and alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells. Environ Mol Mutagen. 2009 Mar;50(2):134-44.