Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAYZZE6)

• DOT Name: Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1)
• Synonyms: EC 1.2.1.5; ALDHIII; Aldehyde dehydrogenase 3; Aldehyde dehydrogenase family 3 member A1
• Gene Name: ALDH3A1
• Related Disease:
  Asthma
  Hepatocellular carcinoma
  Lung neoplasm
  Adult glioblastoma
  Breast adenocarcinoma
  Breast carcinoma
  Cataract
  Cataract 20 multiple types
  Colon cancer
  Colon carcinoma
  Depression
  Glioblastoma multiforme
  Lung cancer
  Lung carcinoma
  Melanoma
  Metastatic malignant neoplasm
  Neoplasm
  Schizophrenia
  Sjogren-Larsson syndrome
  Gastric neoplasm
  Head-neck squamous cell carcinoma
  Hemorrhagic cystitis
  Lung adenocarcinoma
  Advanced cancer
  Breast cancer
  Carcinoma
  Fetal growth restriction
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
• UniProt ID: AL3A1_HUMAN
• PDB ID: 3SZA; 3SZB; 4H80; 4L1O; 4L2O; 8BB8
• EC Number: 1.2.1.5
• Pfam ID: PF00171
• Sequence:
  MSKISEAVKRARAAFSSGRTRPLQFRIQQLEALQRLIQEQEQELVGALAADLHKNEWNAY
  YEEVVYVLEEIEYMIQKLPEWAADEPVEKTPQTQQDELYIHSEPLGVVLVIGTWNYPFNL
  TIQPMVGAIAAGNSVVLKPSELSENMASLLATIIPQYLDKDLYPVINGGVPETTELLKER
  FDHILYTGSTGVGKIIMTAAAKHLTPVTLELGGKSPCYVDKNCDLDVACRRIAWGKFMNS
  GQTCVAPDYILCDPSIQNQIVEKLKKSLKEFYGEDAKKSRDYGRIISARHFQRVMGLIEG
  QKVAYGGTGDAATRYIAPTILTDVDPQSPVMQEEIFGPVLPIVCVRSLEEAIQFINQREK
  PLALYMFSSNDKVIKKMIAETSSGGVAANDVIVHITLHSLPFGGVGNSGMGSYHGKKSFE
  TFSHRRSCLVRPLMNDEGLKVRYPPSPAKMTQH
• Function: ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde (Probable). They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation (Probable). Oxidizes medium and long chain aldehydes into non-toxic fatty acids. Preferentially oxidizes aromatic aldehyde substrates. Comprises about 50 percent of corneal epithelial soluble proteins. May play a role in preventing corneal damage caused by ultraviolet light.
• Tissue Specificity: High levels in stomach, esophagus and lung; low level in the liver and kidney.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Histidine metabolism (hsa00340)
  Tyrosine metabolism (hsa00350)
  Phenylalanine metabolism (hsa00360)
  beta-Alanine metabolism (hsa00410)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Phase I - Functionalization of compounds (R-HSA-211945)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[2]
Lung neoplasm	DISVARNB	Definitive	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Breast adenocarcinoma	DISMPHJ0	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Cataract	DISUD7SL	Strong	Biomarker	[7]
Cataract 20 multiple types	DISN0IHS	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Altered Expression	[8]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[8]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Melanoma	DIS1RRCY	Strong	Altered Expression	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[11]
Schizophrenia	DISSRV2N	Strong	Biomarker	[12]
Sjogren-Larsson syndrome	DISP943Y	Strong	Genetic Variation	[13]
Gastric neoplasm	DISOKN4Y	moderate	Altered Expression	[14]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[14]
Hemorrhagic cystitis	DIS3UA8E	moderate	Genetic Variation	[15]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[16]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[17]
Breast cancer	DIS7DPX1	Limited	Biomarker	[10]
Carcinoma	DISH9F1N	Limited	Biomarker	[18]
Fetal growth restriction	DIS5WEJ5	Limited	Altered Expression	[19]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[3]
Prostate cancer	DISF190Y	Limited	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[18]

This DOT Affected the Drug Response of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) decreases the response to substance of Arsenic trioxide.	[44]
Etoposide	DMNH3PG	Approved	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) affects the response to substance of Etoposide.	[45]
Mitomycin	DMH0ZJE	Approved	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) affects the response to substance of Mitomycin.	[45]
Cyclophosphamide	DM4O2Z7	Approved	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) affects the response to substance of Cyclophosphamide.	[15]
Thiotepa	DMIZKOP	Approved	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) affects the response to substance of Thiotepa.	[15]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) decreases the response to substance of 4-hydroxy-2-nonenal.	[49]
Hexylacrolein	DMBC8KM	Investigative	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) decreases the response to substance of Hexylacrolein.	[49]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Disulfiram	DMCL2OK	Phase 2 Trial	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) increases the metabolism of Disulfiram.	[47]

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaldehyde	DMJFKG4	Investigative	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) increases the oxidation of Acetaldehyde.	[48]
Nitrophenyl acetate	DMHSD8A	Investigative	Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) increases the hydrolysis of Nitrophenyl acetate.	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[35]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[38]

20 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, dimeric NADP-preferring (ALDH3A1).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the activity of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[25]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[26]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[27]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[28]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[29]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[30]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[31]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[32]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[33]
ME-344	DM6JN19	Phase 1/2	ME-344 increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[34]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[36]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[39]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[40]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[41]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[42]
(E)-10-nitrooctadec-9-enoic acid	DMTF7JA	Investigative	(E)-10-nitrooctadec-9-enoic acid decreases the expression of Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1).	[43]

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