Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRJ6OHY)

• DOT Name: Transmembrane protein 100 (TMEM100)
• Gene Name: TMEM100
• Related Disease:
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Stomach cancer
  Advanced cancer
  Hepatocellular carcinoma
  Non-small-cell lung cancer
• UniProt ID: TM100_HUMAN
• Pfam ID: PF16311
• Sequence:
  MTEEPIKEILGAPKAHMAATMEKSPKSEVVITTVPLVSEIQLMAATGGTELSCYRCIIPF
  AVVVFIAGIVVTAVAYSFNSHGSIISIFGLVVLSSGLFLLASSALCWKVRQRSKKAKRRE
  SQTALVANQRSLFA
• Function: Plays a role during embryonic arterial endothelium differentiation and vascular morphogenesis through the ACVRL1 receptor-dependent signaling pathway upon stimulation by bone morphogenetic proteins, such as GDF2/BMP9 and BMP10. Involved in the regulation of nociception, acting as a modulator of the interaction between TRPA1 and TRPV1, two molecular sensors and mediators of pain signals in dorsal root ganglia (DRG) neurons. Mechanistically, it weakens their interaction, thereby releasing the inhibition of TRPA1 by TRPV1 and increasing the single-channel open probability of the TRPA1-TRPV1 complex.
• Tissue Specificity: Expressed in neurons of the myenteric and submucosal plexuses in the gastric body, jejunum and proximal colon. Expressed in arterial endothelial cells and neurons of the central nervous system and peripheral nervous system. Expressed in umbilical artery endothelial cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[1]

12 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 Transmembrane protein 100 (TMEM100).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 100 (TMEM100).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transmembrane protein 100 (TMEM100).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein 100 (TMEM100).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transmembrane protein 100 (TMEM100).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transmembrane protein 100 (TMEM100).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transmembrane protein 100 (TMEM100).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Transmembrane protein 100 (TMEM100).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transmembrane protein 100 (TMEM100).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein 100 (TMEM100).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transmembrane protein 100 (TMEM100).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transmembrane protein 100 (TMEM100).	[15]

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 Transmembrane protein 100 (TMEM100).	[12]

References

• [1] TMEM100 expression suppresses metastasis and enhances sensitivity to chemotherapy in gastric cancer.Biol Chem. 2020 Feb 25;401(2):285-296. doi: 10.1515/hsz-2019-0161.
• [2] Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue.Int J Cancer. 2012 Sep 1;131(5):E643-8. doi: 10.1002/ijc.27426. Epub 2012 Feb 28.
• [3] Low-expression of TMEM100 is associated with poor prognosis in non-small-cell lung cancer.Am J Transl Res. 2017 May 15;9(5):2567-2578. eCollection 2017.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] 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.
• [13] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [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.