Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO1DV7F)

• DOT Name: Alcohol dehydrogenase 1C (ADH1C)
• Synonyms: EC 1.1.1.1; Alcohol dehydrogenase subunit gamma
• Gene Name: ADH1C
• UniProt ID: ADH1G_HUMAN
• PDB ID: 1HT0; 1U3W
• EC Number: 1.1.1.1
• Pfam ID: PF08240 ; PF00107
• Sequence:
  MSTAGKVIKCKAAVLWELKKPFSIEEVEVAPPKAHEVRIKMVAAGICRSDEHVVSGNLVT
  PLPVILGHEAAGIVESVGEGVTTVKPGDKVIPLFTPQCGKCRICKNPESNYCLKNDLGNP
  RGTLQDGTRRFTCSGKPIHHFVGVSTFSQYTVVDENAVAKIDAASPLEKVCLIGCGFSTG
  YGSAVKVAKVTPGSTCAVFGLGGVGLSVVMGCKAAGAARIIAVDINKDKFAKAKELGATE
  CINPQDYKKPIQEVLKEMTDGGVDFSFEVIGRLDTMMASLLCCHEACGTSVIVGVPPDSQ
  NLSINPMLLLTGRTWKGAIFGGFKSKESVPKLVADFMAKKFSLDALITNILPFEKINEGF
  DLLRSGKSIRTVLTF
• Function: Alcohol dehydrogenase. Exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism.
• 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)
  RA biosynthesis pathway (R-HSA-5365859)

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 1C (ADH1C) increases the oxidation of Polyethylene glycol.	[15]
2-Propanol, Isopropanol	DML5O0H	Investigative	Alcohol dehydrogenase 1C (ADH1C) increases the oxidation of 2-Propanol, Isopropanol.	[15]

17 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 1C (ADH1C).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Alcohol dehydrogenase 1C (ADH1C).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Alcohol dehydrogenase 1C (ADH1C).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alcohol dehydrogenase 1C (ADH1C).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Alcohol dehydrogenase 1C (ADH1C).	[2]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Alcohol dehydrogenase 1C (ADH1C).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Alcohol dehydrogenase 1C (ADH1C).	[6]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Alcohol dehydrogenase 1C (ADH1C).	[7]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Alcohol dehydrogenase 1C (ADH1C).	[8]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Alcohol dehydrogenase 1C (ADH1C).	[9]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Alcohol dehydrogenase 1C (ADH1C).	[7]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Alcohol dehydrogenase 1C (ADH1C).	[10]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Alcohol dehydrogenase 1C (ADH1C).	[11]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of Alcohol dehydrogenase 1C (ADH1C).	[12]
Omeprazole	DM471KJ	Approved	Omeprazole decreases the expression of Alcohol dehydrogenase 1C (ADH1C).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Alcohol dehydrogenase 1C (ADH1C).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Alcohol dehydrogenase 1C (ADH1C).	[14]

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] 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.
• [5] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] 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.
• [8] 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.
• [9] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [10] Evaluation of gene induction of drug-metabolizing enzymes and transporters in primary culture of human hepatocytes using high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi. 2002 May;122(5):339-61.
• [11] Proteomics analysis of the proliferative effect of low-dose ouabain on human endothelial cells. Biol Pharm Bull. 2007 Feb;30(2):247-53. doi: 10.1248/bpb.30.247.
• [12] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [13] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] 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.