Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLO5JJ7)

• DOT Name: Zinc finger protein 589
• Synonyms: Stem cell zinc finger protein 1
• Gene Name: ZNF589
• Related Disease: Complex neurodevelopmental disorder
• UniProt ID: ZN589_HUMAN
• Pfam ID: PF01352 ; PF00096 ; PF21225
• Sequence:
  MWAPREQLLGWTAEALPAKDSAWPWEEKPRYLGPVTFEDVAVLFTEAEWKRLSLEQRNLY
  KEVMLENLRNLVSLAESKPEVHTCPSCPLAFGSQQFLSQDELHNHPIPGFHAGNQLHPGN
  PCPEDQPQSQHPSDKNHRGAEAEDQRVEGGVRPLFWSTNERGALVGFSSLFQRPPISSWG
  GNRILEIQLSPAQNASSEEVDRISKRAETPGFGAVTFGECALAFNQKSNLFRQKAVTAEK
  SSDKRQSQVCRECGRGFSRKSQLIIHQRTHTGEKPYVCGECGRGFIVESVLRNHLSTHSG
  EKPYVCSHCGRGFSCKPYLIRHQRTHTREKSFMCTVCGRGFREKSELIKHQRIHTGDKPY
  VCRD
• Function: May play a role in hematopoietic stem/progenitor cell differentiation. May play a role as a DNA binding-dependent transcriptional repressor.
• Tissue Specificity: Isoform 2 is widely expressed. Isoform 3 is only expressed in CD34(+) cells.
• KEGG Pathway: Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway: Generic Transcription Pathway (R-HSA-212436)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Zinc finger protein 589.	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Zinc finger protein 589.	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Zinc finger protein 589.	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Zinc finger protein 589.	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Zinc finger protein 589.	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Zinc finger protein 589.	[7]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Zinc finger protein 589.	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Zinc finger protein 589.	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Zinc finger protein 589.	[10]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Zinc finger protein 589.	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Zinc finger protein 589.	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Zinc finger protein 589.	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Zinc finger protein 589.	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Zinc finger protein 589.	[15]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Zinc finger protein 589.	[16]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Zinc finger protein 589.	[17]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2. Am J Respir Cell Mol Biol. 2008 Sep;39(3):312-23. doi: 10.1165/rcmb.2008-0012OC. Epub 2008 Apr 17.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [17] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.