Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTINY3MW)

• DOT Name: 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1)
• Synonyms: EC 1.2.1.32; Aldehyde dehydrogenase 12; Aldehyde dehydrogenase family 8 member A1
• Gene Name: ALDH8A1
• UniProt ID: AL8A1_HUMAN
• EC Number: 1.2.1.32
• Pfam ID: PF00171
• Sequence:
  MAGTNALLMLENFIDGKFLPCSSYIDSYDPSTGEVYCRVPNSGKDEIEAAVKAAREAFPS
  WSSRSPQERSRVLNQVADLLEQSLEEFAQAESKDQGKTLALARTMDIPRSVQNFRFFASS
  SLHHTSECTQMDHLGCMHYTVRAPVGVAGLISPWNLPLYLLTWKIAPAMAAGNTVIAKPS
  ELTSVTAWMLCKLLDKAGVPPGVVNIVFGTGPRVGEALVSHPEVPLISFTGSQPTAERIT
  QLSAPHCKKLSLELGGKNPAIIFEDANLDECIPATVRSSFANQGEICLCTSRIFVQKSIY
  SEFLKRFVEATRKWKVGIPSDPLVSIGALISKAHLEKVRSYVKRALAEGAQIWCGEGVDK
  LSLPARNQAGYFMLPTVITDIKDESCCMTEEIFGPVTCVVPFDSEEEVIERANNVKYGLA
  ATVWSSNVGRVHRVAKKLQSGLVWTNCWLIRELNLPFGGMKSSGIGREGAKDSYDFFTEI
  KTITVKH
• Function: Catalyzes the NAD-dependent oxidation of 2-aminomuconic semialdehyde of the kynurenine metabolic pathway in L-tryptophan degradation.
• Tissue Specificity: Highly expressed in adult kidney and liver. Detected at lower levels in fetal liver and kidney.
• KEGG Pathway:
  Tryptophan metabolism (hsa00380)
  Metabolic pathways (hsa01100)
• Reactome Pathway: RA biosynthesis pathway (R-HSA-5365859)
• BioCyc Pathway: MetaCyc:ENSG00000118514-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[7]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[8]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[9]
Lindane	DMB8CNL	Approved	Lindane increases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[10]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[11]
Racecadotril	DMFOTZ7	Approved	Racecadotril decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[12]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[13]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[10]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the expression of 2-aminomuconic semialdehyde dehydrogenase (ALDH8A1).	[4]

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] 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.
• [4] Successful validation of genomic biomarkers for human immunotoxicity in Jurkat T cells in vitro. J Appl Toxicol. 2015 Jul;35(7):831-41.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] Xenobiotic CAR activators induce Dlk1-Dio3 locus noncoding RNA expression in mouse liver. Toxicol Sci. 2017 Aug 1;158(2):367-378.
• [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] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [9] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [10] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [11] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [14] Identification of AhR-regulated genes involved in PAH-induced immunotoxicity using a highly-sensitive DNA chip, 3D-Gene human immunity and metabolic syndrome 9k. Toxicol In Vitro. 2010 Feb;24(1):85-91.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.