Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO2DPGL)

• DOT Name: Choline dehydrogenase, mitochondrial (CHDH)
• Synonyms: CDH; CHD; EC 1.1.99.1
• Gene Name: CHDH
• UniProt ID: CHDH_HUMAN
• EC Number: 1.1.99.1
• Pfam ID: PF05199 ; PF00732
• Sequence:
  MWCLLRGLGRPGALARGALGQQQSLGARALASAGSESRDEYSYVVVGAGSAGCVLAGRLT
  EDPAERVLLLEAGPKDVLAGSKRLSWKIHMPAALVANLCDDRYNWCYHTEVQRGLDGRVL
  YWPRGRVWGGSSSLNAMVYVRGHAEDYERWQRQGARGWDYAHCLPYFRKAQGHELGASRY
  RGADGPLRVSRGKTNHPLHCAFLEATQQAGYPLTEDMNGFQQEGFGWMDMTIHEGKRWSA
  ACAYLHPALSRTNLKAEAETLVSRVLFEGTRAVGVEYVKNGQSHRAYASKEVILSGGAIN
  SPQLLMLSGIGNADDLKKLGIPVVCHLPGVGQNLQDHLEIYIQQACTRPITLHSAQKPLR
  KVCIGLEWLWKFTGEGATAHLETGGFIRSQPGVPHPDIQFHFLPSQVIDHGRVPTQQEAY
  QVHVGPMRGTSVGWLKLRSANPQDHPVIQPNYLSTETDIEDFRLCVKLTREIFAQEALAP
  FRGKELQPGSHIQSDKEIDAFVRAKADSAYHPSCTCKMGQPSDPTAVVDPQTRVLGVENL
  RVVDASIMPSMVSGNLNAPTIMIAEKAADIIKGQPALWDKDVPVYKPRTLATQR
• KEGG Pathway:
  Glycine, serine and threonine metabolism (hsa00260)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Choline catabolism (R-HSA-6798163)
• BioCyc Pathway: MetaCyc:HS00375-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Choline dehydrogenase, mitochondrial (CHDH) affects the metabolism of Arsenic.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Choline	DM5D9YK	Investigative	Choline dehydrogenase, mitochondrial (CHDH) affects the response to substance of Choline.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Choline dehydrogenase, mitochondrial (CHDH).	[11]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Choline dehydrogenase, mitochondrial (CHDH).	[11]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Choline dehydrogenase, mitochondrial (CHDH).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Choline dehydrogenase, mitochondrial (CHDH).	[18]

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 Choline dehydrogenase, mitochondrial (CHDH).	[14]

References

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• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] 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.
• [9] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [12] Mitochondrial dysfunction induced by leflunomide and its active metabolite. Toxicology. 2018 Mar 1;396-397:33-45.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] 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.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions. Mutat Res. 2009 Jul 10;667(1-2):4-14. doi: 10.1016/j.mrfmmm.2008.07.003. Epub 2008 Jul 17.
• [20] Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not. Am J Clin Nutr. 2007 Jul;86(1):230-9. doi: 10.1093/ajcn/86.1.230.