Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9MZ4QO)

• DOT Name: Oxidoreductase HTATIP2 (HTATIP2)
• Synonyms: EC 1.1.1.-; 30 kDa HIV-1 TAT-interacting protein; HIV-1 TAT-interactive protein 2
• Gene Name: HTATIP2
• UniProt ID: HTAI2_HUMAN
• PDB ID: 2BKA
• EC Number: 1.1.1.-
• Pfam ID: PF13460
• Sequence:
  MAETEALSKLREDFRMQNKSVFILGASGETGRVLLKEILEQGLFSKVTLIGRRKLTFDEE
  AYKNVNQEVVDFEKLDDYASAFQGHDVGFCCLGTTRGKAGAEGFVRVDRDYVLKSAELAK
  AGGCKHFNLLSSKGADKSSNFLYLQVKGEVEAKVEELKFDRYSVFRPGVLLCDRQESRPG
  EWLVRKFFGSLPDSWASGHSVPVVTVVRAMLNNVVRPRDKQMELLENKAIHDLGKAHGSL
  KP
• Function: Oxidoreductase required for tumor suppression. NADPH-bound form inhibits nuclear import by competing with nuclear import substrates for binding to a subset of nuclear transport receptors. May act as a redox sensor linked to transcription through regulation of nuclear import. Isoform 1 is a metastasis suppressor with proapoptotic as well as antiangiogenic properties. Isoform 2 has an antiapoptotic effect.
• Tissue Specificity: Ubiquitous. Highest level in liver. High levels in lung, skeletal muscle, pancreas and placenta. Moderate levels in heart and kidney. Low levels in brain. Not expressed or low levels in variant small cell lung carcinomas, 33% of hepatocellular carcinomas and neuroblastomas.

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
Etoposide	DMNH3PG	Approved	Oxidoreductase HTATIP2 (HTATIP2) affects the response to substance of Etoposide.	[23]
Topotecan	DMP6G8T	Approved	Oxidoreductase HTATIP2 (HTATIP2) affects the response to substance of Topotecan.	[23]

24 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 Oxidoreductase HTATIP2 (HTATIP2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Oxidoreductase HTATIP2 (HTATIP2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[10]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Oxidoreductase HTATIP2 (HTATIP2).	[11]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[12]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[13]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Oxidoreductase HTATIP2 (HTATIP2).	[2]
Propofol	DMB4OLE	Approved	Propofol increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[14]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[15]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[21]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Oxidoreductase HTATIP2 (HTATIP2).	[22]

References

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• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [7] 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.
• [8] 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [11] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [12] Malathion induced cancer-linked gene expression in human lymphocytes. Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
• [13] 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.
• [14] The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence. Cell Biol Toxicol. 2023 Aug;39(4):1561-1575. doi: 10.1007/s10565-022-09747-9. Epub 2022 Aug 12.
• [15] 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.
• [16] Molecular mechanisms of action of angiopreventive anti-oxidants on endothelial cells: microarray gene expression analyses. Mutat Res. 2005 Dec 11;591(1-2):198-211.
• [17] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [18] 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.
• [19] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [20] 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.
• [21] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [22] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.
• [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.