Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4UHDB5)

• DOT Name: Transcription elongation factor A protein-like 9 (TCEAL9)
• Synonyms: TCEA-like protein 9; Transcription elongation factor S-II protein-like 9; WW domain-binding protein 5; WBP-5
• Gene Name: TCEAL9
• Related Disease:
  Thyroid gland papillary carcinoma
  Neoplasm
  Small-cell lung cancer
• UniProt ID: TCAL9_HUMAN
• Pfam ID: PF04538
• Sequence:
  MKSCQKMEGKPENESEPKHEEEPKPEEKPEEEEKLEEEAKAKGTFRERLIQSLQEFKEDI
  HNRHLSNEDMFREVDEIDEIRRVRNKLIVMRWKVNRNHPYPYLM
• Function: May be involved in transcriptional regulation.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]
Small-cell lung cancer	DISK3LZD	moderate	Altered Expression	[2]

10 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 Transcription elongation factor A protein-like 9 (TCEAL9).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcription elongation factor A protein-like 9 (TCEAL9).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription elongation factor A protein-like 9 (TCEAL9).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription elongation factor A protein-like 9 (TCEAL9).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcription elongation factor A protein-like 9 (TCEAL9).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transcription elongation factor A protein-like 9 (TCEAL9).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transcription elongation factor A protein-like 9 (TCEAL9).	[9]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Transcription elongation factor A protein-like 9 (TCEAL9).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription elongation factor A protein-like 9 (TCEAL9).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Transcription elongation factor A protein-like 9 (TCEAL9).	[13]

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 increases the methylation of Transcription elongation factor A protein-like 9 (TCEAL9).	[11]

References

• [1] Clinicopathological and Prognostic Significance of WW Domain Binding Protein 5 Expression in Papillary Thyroid Carcinoma.Biomed Res Int. 2019 Nov 19;2019:1791065. doi: 10.1155/2019/1791065. eCollection 2019.
• [2] WW domain binding protein 5 induces multidrug resistance of small cell lung cancer under the regulation of miR-335 through the Hippo pathway.Br J Cancer. 2016 Jul 12;115(2):243-51. doi: 10.1038/bjc.2016.186. Epub 2016 Jun 23.
• [3] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [9] 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.
• [10] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [11] 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.
• [12] 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.
• [13] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.