Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKJ9I3N)

• DOT Name: Aldehyde dehydrogenase, mitochondrial (ALDH2)
• Synonyms: EC 1.2.1.3; ALDH class 2; ALDH-E2; ALDHI
• Gene Name: ALDH2
• UniProt ID: ALDH2_HUMAN
• PDB ID: 1CW3; 1NZW; 1NZX; 1NZZ; 1O00; 1O01; 1O02; 1O04; 1O05; 1ZUM; 2ONM; 2ONN; 2ONO; 2ONP; 2VLE; 3INJ; 3INL; 3N80; 3N81; 3N82; 3N83; 3SZ9; 4FQF; 4FR8; 4KWF; 4KWG; 5L13; 8DR9
• EC Number: 1.2.1.3
• Pfam ID: PF00171
• Sequence:
  MLRAAARFGPRLGRRLLSAAATQAVPAPNQQPEVFCNQIFINNEWHDAVSRKTFPTVNPS
  TGEVICQVAEGDKEDVDKAVKAARAAFQLGSPWRRMDASHRGRLLNRLADLIERDRTYLA
  ALETLDNGKPYVISYLVDLDMVLKCLRYYAGWADKYHGKTIPIDGDFFSYTRHEPVGVCG
  QIIPWNFPLLMQAWKLGPALATGNVVVMKVAEQTPLTALYVANLIKEAGFPPGVVNIVPG
  FGPTAGAAIASHEDVDKVAFTGSTEIGRVIQVAAGSSNLKRVTLELGGKSPNIIMSDADM
  DWAVEQAHFALFFNQGQCCCAGSRTFVQEDIYDEFVERSVARAKSRVVGNPFDSKTEQGP
  QVDETQFKKILGYINTGKQEGAKLLCGGGIAADRGYFIQPTVFGDVQDGMTIAKEEIFGP
  VMQILKFKTIEEVVGRANNSTYGLAAAVFTKDLDKANYLSQALQAGTVWVNCYDVFGAQS
  PFGGYKMSGSGRELGEYGLQAYTEVKTVTVKVPQKNS
• Function: Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage.
• 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:
  Smooth Muscle Contraction (R-HSA-445355)
  Ethanol oxidation (R-HSA-71384)
  Metabolism of serotonin (R-HSA-380612)
• BioCyc Pathway: MetaCyc:MONOMER66-302

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Aldehyde dehydrogenase, mitochondrial (ALDH2) decreases the response to substance of Doxorubicin.	[19]
Mitoxantrone	DMM39BF	Approved	Aldehyde dehydrogenase, mitochondrial (ALDH2) affects the response to substance of Mitoxantrone.	[28]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	Investigative	Aldehyde dehydrogenase, mitochondrial (ALDH2) affects the binding of Nicotinamide-Adenine-Dinucleotide.	[33]

This DOT Affected the Regulation of Drug Effects of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Formaldehyde	DM7Q6M0	Investigative	Aldehyde dehydrogenase, mitochondrial (ALDH2) increases the metabolism of Formaldehyde.	[29]
Acetaldehyde	DMJFKG4	Investigative	Aldehyde dehydrogenase, mitochondrial (ALDH2) decreases the metabolism of Acetaldehyde.	[30]
All-trans-retinal	DM6CEVB	Investigative	Aldehyde dehydrogenase, mitochondrial (ALDH2) increases the metabolism of All-trans-retinal.	[32]
Decanal	DMWZKLM	Investigative	Aldehyde dehydrogenase, mitochondrial (ALDH2) increases the metabolism of Decanal.	[32]

This DOT Affected the Biotransformations of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Aldehyde dehydrogenase, mitochondrial (ALDH2) increases the oxidation of 4-hydroxy-2-nonenal.	[31]
acrolein	DMAMCSR	Investigative	Aldehyde dehydrogenase, mitochondrial (ALDH2) increases the oxidation of acrolein.	[31]
Nitrophenyl acetate	DMHSD8A	Investigative	Aldehyde dehydrogenase, mitochondrial (ALDH2) increases the hydrolysis of Nitrophenyl acetate.	[34]

26 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, mitochondrial (ALDH2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[13]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[14]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[15]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[16]
Imatinib	DM7RJXL	Approved	Imatinib decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[17]
Glyceryl trinitrate	DMF72W3	Phase 4	Glyceryl trinitrate decreases the activity of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[14]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram decreases the activity of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[25]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[26]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[27]

2 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 Aldehyde dehydrogenase, mitochondrial (ALDH2).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Aldehyde dehydrogenase, mitochondrial (ALDH2).	[22]

References

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