Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1ZXC66)

• DOT Name: Transmembrane reductase CYB561D2 (CYB561D2)
• Synonyms: EC 7.2.1.3; Cytochrome b561 domain-containing protein 2; Putative tumor suppressor protein 101F6
• Gene Name: CYB561D2
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: C56D2_HUMAN
• EC Number: 7.2.1.3
• Pfam ID: PF03188
• Sequence:
  MALSAETESHIYRALRTASGAAAHLVALGFTIFVAVLARPGSSLFSWHPVLMSLAFSFLM
  TEALLVFSPESSLLHSLSRKGRARCHWVLQLLALLCALLGLGLVILHKEQLGKAHLVTRH
  GQAGLLAVLWAGLQCSGGVGLLYPKLLPRWPLAKLKLYHATSGLVGYLLGSASLLLGMCS
  LWFTASVTGAAWYLAVLCPVLTSLVIMNQVSNAYLYRKRIQP
• Function: Transmembrane reductase that may use ascorbate as an electron donor in the cytoplasm and transfer electrons across endoplasmic reticulum membranes to reduce monodehydro-L-ascorbate radical and iron cations Fe(3+) in the lumen of that compartment.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Biomarker	[1]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Transmembrane reductase CYB561D2 (CYB561D2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane reductase CYB561D2 (CYB561D2).	[10]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane reductase CYB561D2 (CYB561D2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane reductase CYB561D2 (CYB561D2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane reductase CYB561D2 (CYB561D2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transmembrane reductase CYB561D2 (CYB561D2).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transmembrane reductase CYB561D2 (CYB561D2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transmembrane reductase CYB561D2 (CYB561D2).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Transmembrane reductase CYB561D2 (CYB561D2).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transmembrane reductase CYB561D2 (CYB561D2).	[9]

References

• [1] Tumor suppressor 101F6 and ascorbate synergistically and selectively inhibit non-small cell lung cancer growth by caspase-independent apoptosis and autophagy.Cancer Res. 2007 Jul 1;67(13):6293-303. doi: 10.1158/0008-5472.CAN-06-3884.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] 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.