Details of Drug Off-Target (DOT)

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

• DOT Name: Aldehyde dehydrogenase 1A1 (ALDH1A1)
• Synonyms: EC 1.2.1.19; EC 1.2.1.28; EC 1.2.1.3; EC 1.2.1.36; 3-deoxyglucosone dehydrogenase; ALDH-E1; ALHDII; Aldehyde dehydrogenase family 1 member A1; Aldehyde dehydrogenase, cytosolic; Retinal dehydrogenase 1; RALDH 1; RalDH1
• Gene Name: ALDH1A1
• UniProt ID: AL1A1_HUMAN
• PDB ID: 4WB9; 4WJ9; 4WP7; 4WPN; 4X4L; 5AC2; 5L2M; 5L2N; 5L2O; 5TEI; 6DUM; 7JWS; 7JWT; 7JWU; 7JWV; 7JWW; 7UM9; 8D46; 8DNO; 8ENE; 8PVH; 8WFQ
• EC Number: 1.2.1.19; 1.2.1.28; 1.2.1.3; 1.2.1.36
• Pfam ID: PF00171
• Sequence:
  MSSSGTPDLPVLLTDLKIQYTKIFINNEWHDSVSGKKFPVFNPATEEELCQVEEGDKEDV
  DKAVKAARQAFQIGSPWRTMDASERGRLLYKLADLIERDRLLLATMESMNGGKLYSNAYL
  NDLAGCIKTLRYCAGWADKIQGRTIPIDGNFFTYTRHEPIGVCGQIIPWNFPLVMLIWKI
  GPALSCGNTVVVKPAEQTPLTALHVASLIKEAGFPPGVVNIVPGYGPTAGAAISSHMDID
  KVAFTGSTEVGKLIKEAAGKSNLKRVTLELGGKSPCIVLADADLDNAVEFAHHGVFYHQG
  QCCIAASRIFVEESIYDEFVRRSVERAKKYILGNPLTPGVTQGPQIDKEQYDKILDLIES
  GKKEGAKLECGGGPWGNKGYFVQPTVFSNVTDEMRIAKEEIFGPVQQIMKFKSLDDVIKR
  ANNTFYGLSAGVFTKDIDKAITISSALQAGTVWVNCYGVVSAQCPFGGFKMSGNGRELGE
  YGFHEYTEVKTVTVKISQKNS
• Function: Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid. Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid. This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic. Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification. Functions also downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins. Has also an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission.
• Tissue Specificity: Expressed by erythrocytes (at protein level).
• KEGG Pathway:
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Fructose catabolism (R-HSA-70350)
  Ethanol oxidation (R-HSA-71384)
  RA biosynthesis pathway (R-HSA-5365859)
• BioCyc Pathway: MetaCyc:HS09183-MONOMER

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
Fluorouracil	DMUM7HZ	Approved	Aldehyde dehydrogenase 1A1 (ALDH1A1) affects the response to substance of Fluorouracil.	[40]
Thiotepa	DMIZKOP	Approved	Aldehyde dehydrogenase 1A1 (ALDH1A1) affects the response to substance of Thiotepa.	[41]
Hexylacrolein	DMBC8KM	Investigative	Aldehyde dehydrogenase 1A1 (ALDH1A1) decreases the response to substance of Hexylacrolein.	[44]

This DOT Affected the Biotransformations of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaldehyde	DMJFKG4	Investigative	Aldehyde dehydrogenase 1A1 (ALDH1A1) increases the oxidation of Acetaldehyde.	[42]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Aldehyde dehydrogenase 1A1 (ALDH1A1) increases the oxidation of 4-hydroxy-2-nonenal.	[43]
acrolein	DMAMCSR	Investigative	Aldehyde dehydrogenase 1A1 (ALDH1A1) increases the oxidation of acrolein.	[43]
Nitrophenyl acetate	DMHSD8A	Investigative	Aldehyde dehydrogenase 1A1 (ALDH1A1) increases the oxidation of Nitrophenyl acetate.	[32]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[33]

41 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the activity of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[14]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[15]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[16]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[17]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[18]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[10]
Nicotine	DMWX5CO	Approved	Nicotine increases the activity of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[19]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[20]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[21]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[22]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[23]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[24]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[25]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[26]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[10]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[27]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[28]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[31]
Xanthine	DMFBOQ7	Phase 1	Xanthine decreases the activity of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[34]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[22]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[35]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[36]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[37]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[38]
Oleic acid	DM54O1Z	Investigative	Oleic acid decreases the expression of Aldehyde dehydrogenase 1A1 (ALDH1A1).	[39]

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