Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY4AFM1)

• DOT Name: Transcriptional protein SWT1 (SWT1)
• Gene Name: SWT1
• Related Disease:
  Promyelocytic leukaemia
  Hepatitis B virus infection
  leukaemia
  Leukemia
• UniProt ID: SWT1_HUMAN
• Pfam ID: PF13638
• Sequence:
  MSSKESCGKKETSQRKDTTTSSPNFGEKDKKERKTPASSTSSSSIRSVSSEKRKLKSDHT
  DVLYYNIKRRQGLKRLSVEIDTLRRRPKIGSSSQRPIKLKEASYSNDNQIILQSPSSNGT
  KKDIHKCVDFKPKDIKLTNAGSKLDHGIKSLSSPKIASDVKPKAEGQASENKWSHLLVQR
  EKMKELKKGRNSKFRDNSEKCVLEKWKRNQFSQDYNSNKIIKEPLGSRRQKISFKIPIKS
  RDTLQKLVEENVFNIDSNNSKTKQEEREYLESSQVSLNVTRQKTEHLLSDFTYKRTVHEW
  KRKHHYDHQESNDSHSRENLTQSFEAPCCSVSSESIQDADQEMQIVEELHAARVGKSVDL
  PGELMSMEIDLEDDVHSSSANNTSDRKLLIVIDTNILMNHLKFVRILKTTEVPGFDKLVL
  IIPWVVMQELDRMKEGKLLKRAQHKAIPAVHFINDSLKNQDRKLWGQSIQLASQKHYGLS
  DENNDDRVLKCCLQHQELFPCSFVILCTDDRNLRNKGLISGVKSLSKEELSAELLHLSLN
  TDVCHQPCIPKQQLKAETTPLKESYKEESTNSGLSILLESIVSDLEKSLGTGLSSILETE
  MKIAFGNLWMEILYLKPPWTLLHLLQCFKKHWLAVFGLVMEKNLLLTIESLYKNLRKANK
  AVDFTTVKFLLQDSRSLLHAFSTRSNYDGILPQTFAQVNNLLQTFAEVKTKLKPNSSENT
  VTKKQEGTSLKNSHNQEITVFSSSHLPQPSRHQEIWSILESVWITIYQNSTDVFQRLGSN
  SALTTSNIASFEEAFICLQKLMAAVRDILEGIQRILAPNSNYQDVETLYNFLIKYEVNKN
  VKFTAQEIYDCVSQTEYREKLTIGCRQLVEMEYTMQQCNASVYMEAKNRGWCEDMLNYRI
• Tissue Specificity: Expressed weakly in testis.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Promyelocytic leukaemia	DISYGG13	Definitive	Altered Expression	[1]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[2]
leukaemia	DISS7D1V	Strong	Biomarker	[3]
Leukemia	DISNAKFL	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcriptional protein SWT1 (SWT1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcriptional protein SWT1 (SWT1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcriptional protein SWT1 (SWT1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transcriptional protein SWT1 (SWT1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcriptional protein SWT1 (SWT1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transcriptional protein SWT1 (SWT1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcriptional protein SWT1 (SWT1).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transcriptional protein SWT1 (SWT1).	[11]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Transcriptional protein SWT1 (SWT1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Transcriptional protein SWT1 (SWT1).	[13]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of Transcriptional protein SWT1 (SWT1).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transcriptional protein SWT1 (SWT1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Transcriptional protein SWT1 (SWT1).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Transcriptional protein SWT1 (SWT1).	[17]
DZNep	DM0JXBK	Investigative	DZNep decreases the expression of Transcriptional protein SWT1 (SWT1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transcriptional protein SWT1 (SWT1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transcriptional protein SWT1 (SWT1).	[15]

References

• [1] Prevalence and clinical characteristics of N-terminally truncated WT1 expression in acute myeloid leukemia.Leuk Res. 2011 May;35(5):685-8. doi: 10.1016/j.leukres.2011.01.002. Epub 2011 Jan 21.
• [2] Molecular characterization and functional analysis of occult hepatitis B virus infection in Chinese patients infected with genotype C.J Med Virol. 2009 May;81(5):826-35. doi: 10.1002/jmv.21463.
• [3] N-terminally truncated WT1 protein with oncogenic properties overexpressed in leukemia.J Biol Chem. 2006 Sep 22;281(38):28122-30. doi: 10.1074/jbc.M512391200. Epub 2006 May 12.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [12] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [13] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [14] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.