Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXFL7WM)

• DOT Name: Acyl-coenzyme A thioesterase 1 (ACOT1)
• Synonyms: Acyl-CoA thioesterase 1; EC 3.1.2.-; CTE-I; CTE-Ib; Inducible cytosolic acyl-coenzyme A thioester hydrolase; Long chain acyl-CoA thioester hydrolase; Long chain acyl-CoA hydrolase; Palmitoyl-coenzyme A thioesterase; EC 3.1.2.2
• Gene Name: ACOT1
• Related Disease:
  Liver cancer
  Gastric adenocarcinoma
• UniProt ID: ACOT1_HUMAN
• EC Number: 3.1.2.-; 3.1.2.2
• Pfam ID: PF08840 ; PF04775
• Sequence:
  MAATLILEPAGRCCWDEPVRIAVRGLAPEQPVTLRASLRDEKGALFQAHARYRADTLGEL
  DLERAPALGGSFAGLEPMGLLWALEPEKPLVRLVKRDVRTPLAVELEVLDGHDPDPGRLL
  CRVRHERYFLPPGVRREPVRAGRVRGTLFLPPEPGPFPGIVDMFGTGGGLLEYRASLLAG
  KGFAVMALAYYNYEDLPKTMETLHLEYFEEAVNYLLSHPEVKGPGVGLLGISKGGELCLS
  MASFLKGITAAVVINGSVANVGGTLRYKGETLPPVGVNRNRIKVTKDGYADIVDVLNSPL
  EGPDQKSFIPVERAESTFLFLVGQDDHNWKSEFYANEACKRLQAHGRRKPQIICYPETGH
  YIEPPYFPLCRASLHALVGSPIIWGGEPRAHAMAQVDAWKQLQTFFHKHLGGHEGTIPSK
  V
• Function: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. More active towards saturated and unsaturated long chain fatty acyl-CoAs (C12-C20).
• KEGG Pathway:
  Fatty acid elongation (hsa00062)
  Biosynthesis of unsaturated fatty acids (hsa01040)
  Metabolic pathways (hsa01100)
  Ovarian steroidogenesis (hsa04913)
• Reactome Pathway: Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289)
• BioCyc Pathway: MetaCyc:MONOMER-14105

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Gastric adenocarcinoma	DISWWLTC	Limited	Altered Expression	[2]

12 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 1 (ACOT1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[13]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[14]
CITCO	DM0N634	Investigative	CITCO increases the expression of Acyl-coenzyme A thioesterase 1 (ACOT1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Acyl-coenzyme A thioesterase 1 (ACOT1).	[12]

References

• [1] Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.PLoS One. 2014 Jul 24;9(7):e102579. doi: 10.1371/journal.pone.0102579. eCollection 2014.
• [2] ACOT1 expression is associated with poor prognosis in gastric adenocarcinoma.Hum Pathol. 2018 Jul;77:35-44. doi: 10.1016/j.humpath.2018.03.013. Epub 2018 Mar 17.
• [3] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] 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.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] 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.
• [12] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [13] 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.
• [14] Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.