Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTS983E)

• DOT Name: Alcohol dehydrogenase 1A (ADH1A)
• Synonyms: EC 1.1.1.1; Alcohol dehydrogenase subunit alpha
• Gene Name: ADH1A
• UniProt ID: ADH1A_HUMAN
• PDB ID: 1HSO; 1U3T
• EC Number: 1.1.1.1
• Pfam ID: PF08240 ; PF00107
• Sequence:
  MSTAGKVIKCKAAVLWELKKPFSIEEVEVAPPKAHEVRIKMVAVGICGTDDHVVSGTMVT
  PLPVILGHEAAGIVESVGEGVTTVKPGDKVIPLAIPQCGKCRICKNPESNYCLKNDVSNP
  QGTLQDGTSRFTCRRKPIHHFLGISTFSQYTVVDENAVAKIDAASPLEKVCLIGCGFSTG
  YGSAVNVAKVTPGSTCAVFGLGGVGLSAIMGCKAAGAARIIAVDINKDKFAKAKELGATE
  CINPQDYKKPIQEVLKEMTDGGVDFSFEVIGRLDTMMASLLCCHEACGTSVIVGVPPDSQ
  NLSMNPMLLLTGRTWKGAILGGFKSKECVPKLVADFMAKKFSLDALITHVLPFEKINEGF
  DLLHSGKSIRTILMF
• Function: Alcohol dehydrogenase. Oxidizes primary as well as secondary alcohols. Ethanol is a very poor substrate.
• 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:
  RA biosynthesis pathway (R-HSA-5365859)
  Ethanol oxidation (R-HSA-71384)
  Abacavir metabolism (R-HSA-2161541)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Polyethylene glycol	DM4I1JP	Approved	Alcohol dehydrogenase 1A (ADH1A) increases the oxidation of Polyethylene glycol.	[14]
2-Propanol, Isopropanol	DML5O0H	Investigative	Alcohol dehydrogenase 1A (ADH1A) increases the oxidation of 2-Propanol, Isopropanol.	[14]

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 1A (ADH1A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Alcohol dehydrogenase 1A (ADH1A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Alcohol dehydrogenase 1A (ADH1A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Alcohol dehydrogenase 1A (ADH1A).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Alcohol dehydrogenase 1A (ADH1A).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Alcohol dehydrogenase 1A (ADH1A).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Alcohol dehydrogenase 1A (ADH1A).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Alcohol dehydrogenase 1A (ADH1A).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Alcohol dehydrogenase 1A (ADH1A).	[8]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Alcohol dehydrogenase 1A (ADH1A).	[9]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Alcohol dehydrogenase 1A (ADH1A).	[10]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of Alcohol dehydrogenase 1A (ADH1A).	[11]
Clavulanate	DM2FGRT	Approved	Clavulanate decreases the expression of Alcohol dehydrogenase 1A (ADH1A).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Alcohol dehydrogenase 1A (ADH1A).	[13]

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] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [4] Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Arch Toxicol. 2018 Aug;92(8):2517-2531.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [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] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] An in vitro model of human acute ethanol exposure that incorporates CXCR3- and CXCR4-dependent recruitment of immune cells. Toxicol Sci. 2013 Mar;132(1):131-41.
• [10] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [11] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [12] Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol. 2021 Dec;158:112664. doi: 10.1016/j.fct.2021.112664. Epub 2021 Nov 9.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] Oxidation of methanol, ethylene glycol, and isopropanol with human alcohol dehydrogenases and the inhibition by ethanol and 4-methylpyrazole. Chem Biol Interact. 2011 May 30;191(1-3):26-31. doi: 10.1016/j.cbi.2010.12.005. Epub 2010 Dec 15.