Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJZ7E43)

• DOT Name: Zinc finger protein 93
• Synonyms: Zinc finger protein 505; Zinc finger protein HTF34
• Gene Name: ZNF93
• UniProt ID: ZNF93_HUMAN
• PDB ID: 7Z36
• Pfam ID: PF01352 ; PF00096
• Sequence:
  MGPLQFRDVAIEFSLEEWHCLDTAQRNLYRNVMLENYSNLVFLGIVVSKPDLIAHLEQGK
  KPLTMKRHEMVANPSVICSHFAQDLWPEQNIKDSFQKVILRRYEKRGHGNLQLIKRCESV
  DECKVHTGGYNGLNQCSTTTQSKVFQCDKYGKVFHKFSNSNRHNIRHTEKKPFKCIECGK
  AFNQFSTLITHKKIHTGEKPYICEECGKAFKYSSALNTHKRIHTGEKPYKCDKCDKAFIA
  SSTLSKHEIIHTGKKPYKCEECGKAFNQSSTLTKHKKIHTGEKPYKCEECGKAFNQSSTL
  TKHKKIHTGEKPYVCEECGKAFKYSRILTTHKRIHTGEKPYKCNKCGKAFIASSTLSRHE
  FIHMGKKHYKCEECGKAFIWSSVLTRHKRVHTGEKPYKCEECGKAFKYSSTLSSHKRSHT
  GEKPYKCEECGKAFVASSTLSKHEIIHTGKKPYKCEECGKAFNQSSSLTKHKKIHTGEKP
  YKCEECGKAFNQSSSLTKHKKIHTGEKPYKCEECGKAFNQSSTLIKHKKIHTREKPYKCE
  ECGKAFHLSTHLTTHKILHTGEKPYRCRECGKAFNHSATLSSHKKIHSGEKPYECDKCGK
  AFISPSSLSRHEIIHTGEKP
• Function: Transcription factor specifically required to repress long interspersed nuclear element 1 (L1) retrotransposons: recognizes and binds L1 sequences and repress their expression by recruiting a repressive complex containing TRIM28/KAP1. Not able to repress expression of all subtypes of L1 elements. Binds to the 5' end of L1PA4, L1PA5 and L1PA6 subtypes, and some L1PA3 subtypes. Does not bind to L1PA7 or older subtypes nor at the most recently evolved L1PA2 and L1Hs. 50% of L1PA3 elements have lost the ZNF93-binding site, explaining why ZNF93 is not able to repress their expression.
• KEGG Pathway: Herpes simplex virus 1 infection (hsa05168)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Trabectedin	DMG3Y89	Approved	Zinc finger protein 93 decreases the response to substance of Trabectedin.	[11]
PM-00104	DMMKOPX	Phase 2	Zinc finger protein 93 decreases the response to substance of PM-00104.	[11]

10 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 Zinc finger protein 93.	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger protein 93.	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Zinc finger protein 93.	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Zinc finger protein 93.	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Zinc finger protein 93.	[5]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Zinc finger protein 93.	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Zinc finger protein 93.	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Zinc finger protein 93.	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Zinc finger protein 93.	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Zinc finger protein 93.	[10]

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 Zinc finger protein 93.	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] 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.
• [8] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] 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.
• [10] 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.
• [11] ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) in human cancer cell lines. PLoS One. 2009 Sep 9;4(9):e6967. doi: 10.1371/journal.pone.0006967.