Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS7DYH9)

• DOT Name: Alcohol dehydrogenase 6 (ADH6)
• Synonyms: EC 1.1.1.1
• Gene Name: ADH6
• UniProt ID: ADH6_HUMAN
• EC Number: 1.1.1.1
• Pfam ID: PF08240 ; PF00107
• Sequence:
  MSTTGQVIRCKAAILWKPGAPFSIEEVEVAPPKAKEVRIKVVATGLCGTEMKVLGSKHLD
  LLYPTILGHEGAGIVESIGEGVSTVKPGDKVITLFLPQCGECTSCLNSEGNFCIQFKQSK
  TQLMSDGTSRFTCKGKSIYHFGNTSTFCEYTVIKEISVAKIDAVAPLEKVCLISCGFSTG
  FGAAINTAKVTPGSTCAVFGLGGVGLSVVMGCKAAGAARIIGVDVNKEKFKKAQELGATE
  CLNPQDLKKPIQEVLFDMTDAGIDFCFEAIGNLDVLAAALASCNESYGVCVVVGVLPASV
  QLKISGQLFFSGRSLKGSVFGGWKSRQHIPKLVADYMAEKLNLDPLITHTLNLDKINEAV
  ELMKTGKW
• Function: Alcohol dehydrogenase. Catalyzes the NAD-dependent oxidation of primary alcohols to the corresponding aldehydes. Oxidizes secondary alcohols to the corresponding ketones.
• Tissue Specificity: Stomach and liver.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Fatty acid degradation (hsa00071)
  Tyrosine metabolism (hsa00350)
  Pyruvate metabolism (hsa00620)
  Retinol metabolism (hsa00830)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Metabolic pathways (hsa01100)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway: Ethanol oxidation (R-HSA-71384)

Molecular Interaction Atlas (MIA) of This DOT

14 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 Alcohol dehydrogenase 6 (ADH6).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[2]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Alcohol dehydrogenase 6 (ADH6).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Alcohol dehydrogenase 6 (ADH6).	[12]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [8] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.