Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPBW5N5)

• DOT Name: DNA fragmentation factor subunit beta (DFFB)
• Synonyms: EC 3.-.-.-; Caspase-activated deoxyribonuclease; CAD; Caspase-activated DNase; Caspase-activated nuclease; CPAN; DNA fragmentation factor 40 kDa subunit; DFF-40
• Gene Name: DFFB
• UniProt ID: DFFB_HUMAN
• PDB ID: 1IBX
• EC Number: 3.-.-.-
• Pfam ID: PF02017 ; PF09230
• Sequence:
  MLQKPKSVKLRALRSPRKFGVAGRSCQEVLRKGCLRFQLPERGSRLCLYEDGTELTEDYF
  PSVPDNAELVLLTLGQAWQGYVSDIRRFLSAFHEPQVGLIQAAQQLLCDEQAPQRQRLLA
  DLLHNVSQNIAAETRAEDPPWFEGLESRFQSKSGYLRYSCESRIRSYLREVSSYPSTVGA
  EAQEEFLRVLGSMCQRLRSMQYNGSYFDRGAKGGSRLCTPEGWFSCQGPFDMDSCLSRHS
  INPYSNRESRILFSTWNLDHIIEKKRTIIPTLVEAIKEQDGREVDWEYFYGLLFTSENLK
  LVHIVCHKKTTHKLNCDPSRIYKPQTRLKRKQPVRKRQ
• Function: Nuclease that induces DNA fragmentation and chromatin condensation during apoptosis. Degrades naked DNA and induces apoptotic morphology.
• KEGG Pathway: Apoptosis (hsa04210)
• Reactome Pathway: Apoptosis induced DNA fragmentation (R-HSA-140342)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	DNA fragmentation factor subunit beta (DFFB) increases the response to substance of Irinotecan.	[22]
Vinblastine	DM5TVS3	Approved	DNA fragmentation factor subunit beta (DFFB) affects the response to substance of Vinblastine.	[23]
Tributylstannanyl	DMHN7CB	Investigative	DNA fragmentation factor subunit beta (DFFB) increases the response to substance of Tributylstannanyl.	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of DNA fragmentation factor subunit beta (DFFB).	[1]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of DNA fragmentation factor subunit beta (DFFB).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of DNA fragmentation factor subunit beta (DFFB).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DNA fragmentation factor subunit beta (DFFB).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[9]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[11]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[12]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of DNA fragmentation factor subunit beta (DFFB).	[13]
Menthol	DMG2KW7	Approved	Menthol increases the expression of DNA fragmentation factor subunit beta (DFFB).	[14]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[16]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of DNA fragmentation factor subunit beta (DFFB).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[18]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[20]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of DNA fragmentation factor subunit beta (DFFB).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sulindac	DM2QHZU	Approved	Sulindac affects the localization of DNA fragmentation factor subunit beta (DFFB).	[15]

References

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• [6] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
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• [8] Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Ornithine decarboxylase antizyme upregulates DNA-dependent protein kinase and enhances the nonhomologous end-joining repair of DNA double-strand breaks in human oral cancer cells. Biochemistry. 2007 Aug 7;46(31):8920-32. doi: 10.1021/bi7000328. Epub 2007 Jul 14.
• [11] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [12] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [13] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [14] 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.
• [15] Sulindac activates nuclear translocation of AIF, DFF40 and endonuclease G but not induces oligonucleosomal DNA fragmentation in HT-29 cells. Life Sci. 2005 Sep 2;77(16):2059-70. doi: 10.1016/j.lfs.2005.04.021.
• [16] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
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• [19] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
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• [21] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [22] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
• [23] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [24] DNA fragmentation factor 40 expression in T cells confers sensibility to tributyltin-induced apoptosis. Toxicology. 2019 Oct 1;426:152255. doi: 10.1016/j.tox.2019.152255. Epub 2019 Aug 8.