Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWJK2XZ)

• DOT Name: Transmembrane protein 50B (TMEM50B)
• Synonyms: HCV p7-trans-regulated protein 3
• Gene Name: TMEM50B
• Related Disease:
  Advanced cancer
  Thyroid gland papillary carcinoma
• UniProt ID: TM50B_HUMAN
• Pfam ID: PF05255
• Sequence:
  MAGFLDNFRWPECECIDWSERRNAVASVVAGILFFTGWWIMIDAAVVYPKPEQLNHAFHT
  CGVFSTLAFFMINAVSNAQVRGDSYESGCLGRTGARVWLFIGFMLMFGSLIASMWILFGA
  YVTQNTDVYPGLAVFFQNALIFFSTLIYKFGRTEELWT

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Genetic Variation	[1]

14 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 50B (TMEM50B).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 50B (TMEM50B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transmembrane protein 50B (TMEM50B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 50B (TMEM50B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Transmembrane protein 50B (TMEM50B).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 50B (TMEM50B).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 50B (TMEM50B).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transmembrane protein 50B (TMEM50B).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Transmembrane protein 50B (TMEM50B).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Transmembrane protein 50B (TMEM50B).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Transmembrane protein 50B (TMEM50B).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 50B (TMEM50B).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane protein 50B (TMEM50B).	[15]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Transmembrane protein 50B (TMEM50B).	[16]

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 decreases the methylation of Transmembrane protein 50B (TMEM50B).	[12]

References

• [1] A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression.Surgery. 2005 Dec;138(6):1050-6; discussion 1056-7. doi: 10.1016/j.surg.2005.09.010.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [9] 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.
• [10] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [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] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.