Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXW9TE2)

• DOT Name: Aldehyde dehydrogenase X, mitochondrial (ALDH1B1)
• Synonyms: EC 1.2.1.3; Aldehyde dehydrogenase 5; Aldehyde dehydrogenase family 1 member B1
• Gene Name: ALDH1B1
• Related Disease: Complex neurodevelopmental disorder
• UniProt ID: AL1B1_HUMAN
• PDB ID: 7MJC; 7MJD; 7RAD
• EC Number: 1.2.1.3
• Pfam ID: PF00171
• Sequence:
  MLRFLAPRLLSLQGRTARYSSAAALPSPILNPDIPYNQLFINNEWQDAVSKKTFPTVNPT
  TGEVIGHVAEGDRADVDRAVKAAREAFRLGSPWRRMDASERGRLLNRLADLVERDRVYLA
  SLETLDNGKPFQESYALDLDEVIKVYRYFAGWADKWHGKTIPMDGQHFCFTRHEPVGVCG
  QIIPWNFPLVMQGWKLAPALATGNTVVMKVAEQTPLSALYLASLIKEAGFPPGVVNIITG
  YGPTAGAAIAQHVDVDKVAFTGSTEVGHLIQKAAGDSNLKRVTLELGGKSPSIVLADADM
  EHAVEQCHEALFFNMGQCCCAGSRTFVEESIYNEFLERTVEKAKQRKVGNPFELDTQQGP
  QVDKEQFERVLGYIQLGQKEGAKLLCGGERFGERGFFIKPTVFGGVQDDMRIAKEEIFGP
  VQPLFKFKKIEEVVERANNTRYGLAAAVFTRDLDKAMYFTQALQAGTVWVNTYNIVTCHT
  PFGGFKESGNGRELGEDGLKAYTEVKTVTIKVPQKNS
• Function: ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation.
• Tissue Specificity: Liver, testis and to a lesser extent in brain.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Ascorbate and aldarate metabolism (hsa00053)
  Fatty acid degradation (hsa00071)
  Valine, leucine and isoleucine degradation (hsa00280)
  Lysine degradation (hsa00310)
  Arginine and proline metabolism (hsa00330)
  Histidine metabolism (hsa00340)
  Tryptophan metabolism (hsa00380)
  beta-Alanine metabolism (hsa00410)
  Glycerolipid metabolism (hsa00561)
  Pyruvate metabolism (hsa00620)
  Pantothe.te and CoA biosynthesis (hsa00770)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway: Ethanol oxidation (R-HSA-71384)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal dominant	[1]

22 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 Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[13]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[14]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[17]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[21]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Aldehyde dehydrogenase X, mitochondrial (ALDH1B1).	[22]

References

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• [13] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [14] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [15] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [20] 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.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Proteomic analysis of proteins associated with cellular senescence by calorie restriction in mesenchymal stem cells. In Vitro Cell Dev Biol Anim. 2012 Mar;48(3):186-95.