Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWRUST1)

• DOT Name: Acyl-coenzyme A thioesterase 13 (ACOT13)
• Synonyms: Acyl-CoA thioesterase 13; EC 3.1.2.-; Hotdog-fold thioesterase superfamily member 2; Palmitoyl-CoA hydrolase; EC 3.1.2.2; Thioesterase superfamily member 2; THEM2
• Gene Name: ACOT13
• UniProt ID: ACO13_HUMAN
• PDB ID: 2F0X; 2H4U; 3F5O
• EC Number: 3.1.2.-; 3.1.2.2
• Pfam ID: PF03061
• Sequence:
  MTSMTQSLREVIKAMTKARNFERVLGKITLVSAAPGKVICEMKVEEEHTNAIGTLHGGLT
  ATLVDNISTMALLCTERGAPGVSVDMNITYMSPAKLGEDIVITAHVLKQGKTLAFTSVDL
  TNKATGKLIAQGRHTKHLGN
• Function: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. Has acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates. Can also hydrolyze 3-hydroxyphenylacetyl-CoA and 3,4-dihydroxyphenylacetyl-CoA (in vitro). May play a role in controlling adaptive thermogenesis.
• Reactome Pathway: Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Acyl-coenzyme A thioesterase 13 (ACOT13) affects the response to substance of Fluorouracil.	[19]
Vinblastine	DM5TVS3	Approved	Acyl-coenzyme A thioesterase 13 (ACOT13) affects the response to substance of Vinblastine.	[19]

1 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 Acyl-coenzyme A thioesterase 13 (ACOT13).	[1]

18 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 Acyl-coenzyme A thioesterase 13 (ACOT13).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[11]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Acyl-coenzyme A thioesterase 13 (ACOT13).	[18]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] 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.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [10] 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.
• [11] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] 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.
• [16] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [17] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [19] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.