Details of Drug Off-Target (DOT)

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

• DOT Name: Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3)
• Synonyms: EC 1.3.3.6; Branched-chain acyl-CoA oxidase; BRCACox; Pristanoyl-CoA oxidase
• Gene Name: ACOX3
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
• UniProt ID: ACOX3_HUMAN
• EC Number: 1.3.3.6
• Pfam ID: PF01756 ; PF02770
• Sequence:
  MASTVEGGDTALLPEFPRGPLDAYRARASFSWKELALFTEGEGMLRFKKTIFSALENDPL
  FARSPGADLSLEKYRELNFLRCKRIFEYDFLSVEDMFKSPLKVPALIQCLGMYDSSLAAK
  YLLHSLVFGSAVYSSGSERHLTYIQKIFRMEIFGCFALTELSHGSNTKAIRTTAHYDPAT
  EEFIIHSPDFEAAKFWVGNMGKTATHAVVFAKLCVPGDQCHGLHPFIVQIRDPKTLLPMP
  GVMVGDIGKKLGQNGLDNGFAMFHKVRVPRQSLLNRMGDVTPEGTYVSPFKDVRQRFGAS
  LGSLSSGRVSIVSLAILNLKLAVAIALRFSATRRQFGPTEEEEIPVLEYPMQQWRLLPYL
  AAVYALDHFSKSLFLDLVELQRGLASGDRSARQAELGREIHALASASKPLASWTTQQGIQ
  ECREACGGHGYLAMNRLGVLRDDNDPNCTYEGDNNILLQQTSNYLLGLLAHQVHDGACFR
  SPLKSVDFLDAYPGILDQKFEVSSVADCLDSAVALAAYKWLVCYLLRETYQKLNQEKRSG
  SSDFEARNKCQVSHGRPLALAFVELTVVQRFHEHVHQPSVPPSLRAVLGRLSALYALWSL
  SRHAALLYRGGYFSGEQAGEVLESAVLALCSQLKDDAVALVDVIAPPDFVLDSPIGRADG
  ELYKNLWGAVLQESKVLERASWWPEFSVNKPVIGSLKSKL
• Function: Oxidizes the CoA-esters of 2-methyl-branched fatty acids.
• KEGG Pathway:
  Fatty acid degradation (hsa00071)
  beta-Alanine metabolism (hsa00410)
  alpha-Linolenic acid metabolism (hsa00592)
  Propanoate metabolism (hsa00640)
  Biosynthesis of unsaturated fatty acids (hsa01040)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Fatty acid metabolism (hsa01212)
  PPAR sig.ling pathway (hsa03320)
  cAMP sig.ling pathway (hsa04024)
  Peroxisome (hsa04146)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  Peroxisomal protein import (R-HSA-9033241)
  Beta-oxidation of pristanoyl-CoA (R-HSA-389887)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[1]

2 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 Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[9]

8 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 Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[7]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Peroxisomal acyl-coenzyme A oxidase 3 (ACOX3).	[10]

References

• [1] Peroxisomal branched chain fatty acid beta-oxidation pathway is upregulated in prostate cancer.Prostate. 2005 Jun 1;63(4):316-23. doi: 10.1002/pros.20177.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [9] 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.
• [10] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.