Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYDSA49)

• DOT Name: Transmembrane protein 116 (TMEM116)
• Gene Name: TMEM116
• UniProt ID: TM116_HUMAN
• Sequence:
  MKHTQSGQSTSPLVIDYTCRVCQMAFVFSSLIPLLLMTPVFCLGNTSECFQNFSQSHKCI
  LMHSPPSAMAELPPSANTSVCSTLYFYGIAIFLGSFVLSLLTIMVLLIRAQTLYKKFVKS
  TGFLGSEQWAVIHIVDQRVRFYPVAFFCCWGPAVILMIIKLTKPQDTKLHMALYVLQALT
  ATSQGLLNCGVYGWTQHKFHQLKQEARRDADTQTPLLCSQKRFYSRGLNSLESTLTFPAS
  TSTIF

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Transmembrane protein 116 (TMEM116).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transmembrane protein 116 (TMEM116).	[8]

13 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 Transmembrane protein 116 (TMEM116).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transmembrane protein 116 (TMEM116).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 116 (TMEM116).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 116 (TMEM116).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 116 (TMEM116).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 116 (TMEM116).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane protein 116 (TMEM116).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 116 (TMEM116).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Transmembrane protein 116 (TMEM116).	[10]
Nobiletin	DM7R3B6	Preclinical	Nobiletin increases the expression of Transmembrane protein 116 (TMEM116).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transmembrane protein 116 (TMEM116).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Transmembrane protein 116 (TMEM116).	[13]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Transmembrane protein 116 (TMEM116).	[14]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] 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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] 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.
• [9] 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.
• [10] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [11] Characteristics of nobiletin-mediated alteration of gene expression in cultured cell lines. Biochem Biophys Res Commun. 2013 Feb 15;431(3):530-4.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] 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.
• [14] 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.