Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4AS8RJ)

• DOT Name: Transmembrane protein 170B (TMEM170B)
• Gene Name: TMEM170B
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: T170B_HUMAN
• Pfam ID: PF10190
• Sequence:
  MKAEGGDHSMINLSVQQVLSLWAHGTVLRNLTEMWYWIFLWALFSSLFVHGAAGVLMFVM
  LQRHRQGRVISVIAVSIGFLASVTGAMITSAAVAGIYRVAGKNMAPLEALVWGVGQTVLT
  LIISFSRILATL
• Function: Negatively regulates the canonical Wnt signaling in breast cancer cells. Exerts an inhibitory effect on breast cancer growth by inhibiting CTNNB1 stabilization and nucleus translocation, which reduces the activity of Wnt targets.
• Tissue Specificity: Expressed in normal breast tissues. Down-regulated in breast cancer cells (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

18 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 170B (TMEM170B).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 170B (TMEM170B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transmembrane protein 170B (TMEM170B).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 170B (TMEM170B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transmembrane protein 170B (TMEM170B).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transmembrane protein 170B (TMEM170B).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Transmembrane protein 170B (TMEM170B).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Transmembrane protein 170B (TMEM170B).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Transmembrane protein 170B (TMEM170B).	[10]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Transmembrane protein 170B (TMEM170B).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transmembrane protein 170B (TMEM170B).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Transmembrane protein 170B (TMEM170B).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane protein 170B (TMEM170B).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transmembrane protein 170B (TMEM170B).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 170B (TMEM170B).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane protein 170B (TMEM170B).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transmembrane protein 170B (TMEM170B).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 170B (TMEM170B).	[17]

References

• [1] Transmembrane protein 170B is a novel breast tumorigenesis suppressor gene that inhibits the Wnt/-catenin pathway.Cell Death Dis. 2018 Jan 24;9(2):91. doi: 10.1038/s41419-017-0128-y.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] 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.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [12] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [16] 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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.