Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQNFH3E)

• DOT Name: Threonine synthase-like 1 (THNSL1)
• Synonyms: TSH1
• Gene Name: THNSL1
• UniProt ID: THNS1_HUMAN
• Pfam ID: PF01202 ; PF14821
• Sequence:
  MLHFNRCHHLKKITQKCFSSIHVKTDKHAQRFLSRTFALAELRKSWYSTHSLVGDKNIIL
  MGPPGAGKTTVGRIIGQKLGCCVIDVDDDILEKTWNMSVSEKLQDVGNEQFLEEEGKAVL
  NFSASGSVISLTGSNPMHDASMWHLKKNGIIVYLDVPLLDLICRLKLMKTDRIVGQNSGT
  SMKDLLKFRRQYYKKWYDARVFCESGASPEEVADKVLNAIKRYQDVDSETFISTRHVWPE
  DCEQKVSAKFFSEAVIEGLASDGGLFVPAKEFPKLSCGEWKSLVGATYVERAQILLERCI
  HPADIPAARLGEMIETAYGENFACSKIAPVRHLSGNQFILELFHGPTGSFKDLSLQLMPH
  IFAHCIPPSCNYMILVATSGDTGSAVLNGFSRLNKNDKQRIAVVAFFPENGVSDFQKAQI
  IGSQRENGWAVGVESDFDFCQTAIKRIFNDSDFTGFLTVEYGTILSSANSINWGRLLPQV
  VYHASAYLDLVSQGFISFGSPVDVCIPTGNFGNILAAVYAKMMGIPIRKFICASNQNHVL
  TDFIKTGHYDLRERKLAQTFSPSIDILKSSNLERHLHLMANKDGQLMTELFNRLESQHHF
  QIEKALVEKLQQDFVADWCSEGECLAAINSTYNTSGYILDPHTAVAKVVADRVQDKTCPV
  IISSTAHYSKFAPAIMQALKIKEINETSSSQLYLLGSYNALPPLHEALLERTKQQEKMEY
  QVCAADMNVLKSHVEQLVQNQFI

Molecular Interaction Atlas (MIA) of This DOT

16 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 Threonine synthase-like 1 (THNSL1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Threonine synthase-like 1 (THNSL1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Threonine synthase-like 1 (THNSL1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Threonine synthase-like 1 (THNSL1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Threonine synthase-like 1 (THNSL1).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Threonine synthase-like 1 (THNSL1).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Threonine synthase-like 1 (THNSL1).	[7]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Threonine synthase-like 1 (THNSL1).	[8]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Threonine synthase-like 1 (THNSL1).	[9]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Threonine synthase-like 1 (THNSL1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Threonine synthase-like 1 (THNSL1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Threonine synthase-like 1 (THNSL1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Threonine synthase-like 1 (THNSL1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Threonine synthase-like 1 (THNSL1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Threonine synthase-like 1 (THNSL1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Threonine synthase-like 1 (THNSL1).	[16]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [9] 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.
• [10] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] 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.
• [16] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.