Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBOQE6N)

• DOT Name: Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9)
• Synonyms: Acyl-CoA thioesterase 9; EC 3.1.2.-; Acyl-CoA thioester hydrolase 9
• Gene Name: ACOT9
• Related Disease: Intellectual disability
• UniProt ID: ACOT9_HUMAN
• EC Number: 3.1.2.-
• Sequence:
  MRRAALRLCALGKGQLTPGRGLTQGPQNPKKQGIFHIHEVRDKLREIVGASTNWRDHVKA
  MEERKLLHSFLAKSQDGLPPRRMKDSYIEVLLPLGSEPELREKYLTVQNTVRFGRILEDL
  DSLGVLICYMHNKIHSAKMSPLSIVTALVDKIDMCKKSLSPEQDIKFSGHVSWVGKTSME
  VKMQMFQLHGDEFCPVLDATFVMVARDSENKGPAFVNPLIPESPEEEELFRQGELNKGRR
  IAFSSTSLLKMAPSAEERTTIHEMFLSTLDPKTISFRSRVLPSNAVWMENSKLKSLEICH
  PQERNIFNRIFGGFLMRKAYELAWATACSFGGSRPFVVAVDDIMFQKPVEVGSLLFLSSQ
  VCFTQNNYIQVRVHSEVASLQEKQHTTTNVFHFTFMSEKEVPLVFPKTYGESMLYLDGQR
  HFNSMSGPATLRKDYLVEP
• Function: Acyl-CoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. Active on long chain acyl-CoAs.
• Reactome Pathway: Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289)
• BioCyc Pathway: MetaCyc:HS04631-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Limited	Biomarker	[1]

11 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 Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[8]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[13]

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 Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[11]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Acyl-coenzyme A thioesterase 9, mitochondrial (ACOT9).	[14]

References

• [1] Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.Hum Mutat. 2015 Dec;36(12):1197-204. doi: 10.1002/humu.22901. Epub 2015 Sep 30.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [10] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] 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.
• [14] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.