Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTONNAV1)

• DOT Name: Cytochrome b5 type B (CYB5B)
• Synonyms: Cytochrome b5 outer mitochondrial membrane isoform
• Gene Name: CYB5B
• Related Disease:
  Classic Hodgkin lymphoma
  Narcolepsy
• UniProt ID: CYB5B_HUMAN
• PDB ID: 3NER
• Pfam ID: PF00173
• Sequence:
  MSGSMATAEASGSDGKGQEVETSVTYYRLEEVAKRNSLKELWLVIHGRVYDVTRFLNEHP
  GGEEVLLEQAGVDASESFEDVGHSSDAREMLKQYYIGDIHPSDLKPESGSKDPSKNDTCK
  SCWAYWILPIIGAVLLGFLYRYYTSESKSS
• Function: Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases.
• Reactome Pathway: Phase I - Functionalization of compounds (R-HSA-211945)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[1]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Cytochrome b5 type B (CYB5B) affects the binding of PEITC.	[23]

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 Cytochrome b5 type B (CYB5B).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome b5 type B (CYB5B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome b5 type B (CYB5B).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cytochrome b5 type B (CYB5B).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytochrome b5 type B (CYB5B).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytochrome b5 type B (CYB5B).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cytochrome b5 type B (CYB5B).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cytochrome b5 type B (CYB5B).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cytochrome b5 type B (CYB5B).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cytochrome b5 type B (CYB5B).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cytochrome b5 type B (CYB5B).	[13]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Cytochrome b5 type B (CYB5B).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cytochrome b5 type B (CYB5B).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Cytochrome b5 type B (CYB5B).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cytochrome b5 type B (CYB5B).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cytochrome b5 type B (CYB5B).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Cytochrome b5 type B (CYB5B).	[21]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Cytochrome b5 type B (CYB5B).	[22]

2 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 affects the methylation of Cytochrome b5 type B (CYB5B).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cytochrome b5 type B (CYB5B).	[16]

References

• [1] Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B5b (CYB5B).Mol Cancer. 2010 Jan 26;9:14. doi: 10.1186/1476-4598-9-14.
• [2] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] 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.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [14] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [15] 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.
• [16] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [19] 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.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [22] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [23] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.