Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM0A0DY)

• DOT Name: Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1)
• Synonyms: AOX; EC 1.3.3.6; Palmitoyl-CoA oxidase; Peroxisomal fatty acyl-CoA oxidase; Straight-chain acyl-CoA oxidase; SCOX
• Gene Name: ACOX1
• Related Disease:
  Peroxisomal acyl-CoA oxidase deficiency
  Adult lymphoma
  Citrullinemia type II
  Colorectal carcinoma
  Depression
  Fatty liver disease
  Hepatocellular carcinoma
  Lymphoma
  Metabolic disorder
  Mitchell syndrome
  Mitochondrial disease
  Non-alcoholic fatty liver disease
  Pediatric lymphoma
  Stroke
  Leukodystrophy
  Lipid metabolism disorder
  Neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Peroxisomal disorder
• UniProt ID: ACOX1_HUMAN
• EC Number: 1.3.3.6
• Pfam ID: PF01756 ; PF02770 ; PF14749
• Sequence:
  MNPDLRRERDSASFNPELLTHILDGSPEKTRRRREIENMILNDPDFQHEDLNFLTRSQRY
  EVAVRKSAIMVKKMREFGIADPDEIMWFKKLHLVNFVEPVGLNYSMFIPTLLNQGTTAQK
  EKWLLSSKGLQIIGTYAQTEMGHGTHLRGLETTATYDPETQEFILNSPTVTSIKWWPGGL
  GKTSNHAIVLAQLITKGKCYGLHAFIVPIREIGTHKPLPGITVGDIGPKFGYDEIDNGYL
  KMDNHRIPRENMLMKYAQVKPDGTYVKPLSNKLTYGTMVFVRSFLVGEAARALSKACTIA
  IRYSAVRHQSEIKPGEPEPQILDFQTQQYKLFPLLATAYAFQFVGAYMKETYHRINEGIG
  QGDLSELPELHALTAGLKAFTSWTANTGIEACRMACGGHGYSHCSGLPNIYVNFTPSCTF
  EGENTVMMLQTARFLMKSYDQVHSGKLVCGMVSYLNDLPSQRIQPQQVAVWPTMVDINSP
  ESLTEAYKLRAARLVEIAAKNLQKEVIHRKSKEVAWNLTSVDLVRASEAHCHYVVVKLFS
  EKLLKIQDKAIQAVLRSLCLLYSLYGISQNAGDFLQGSIMTEPQITQVNQRVKELLTLIR
  SDAVALVDAFDFQDVTLGSVLGRYDGNVYENLFEWAKNSPLNKAEVHESYKHLKSLQSKL
• Function: Involved in the initial and rate-limiting step of peroxisomal beta-oxidation of straight-chain saturated and unsaturated very-long-chain fatty acids. Catalyzes the desaturation of fatty acyl-CoAs such as palmitoyl-CoA (hexadecanoyl-CoA) to 2-trans-enoyl-CoAs ((2E)-enoyl-CoAs) such as (2E)-hexadecenoyl-CoA, and donates electrons directly to molecular oxygen (O(2)), thereby producing hydrogen peroxide (H(2)O(2)) ; [Isoform 1]: Shows highest activity against medium-chain fatty acyl-CoAs. Shows optimum activity with a chain length of 10 carbons (decanoyl-CoA) in vitro; [Isoform 2]: Is active against a much broader range of substrates and shows activity towards long-chain fatty acyl-CoAs.
• Tissue Specificity: Widely expressed with highest levels of isoform 1 and isoform 2 detected in testis. Isoform 1 is expressed at higher levels than isoform 2 in liver and kidney while isoform 2 levels are higher in brain, lung, muscle, white adipose tissue and testis. Levels are almost equal in heart.
• 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:
  TYSND1 cleaves peroxisomal proteins (R-HSA-9033500)
  Peroxisomal protein import (R-HSA-9033241)
• BioCyc Pathway: MetaCyc:HS08589-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Peroxisomal acyl-CoA oxidase deficiency	DISO6FJN	Definitive	Autosomal recessive	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Citrullinemia type II	DIS2UURN	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Depression	DIS3XJ69	Strong	Altered Expression	[5]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Lymphoma	DISN6V4S	Strong	Biomarker	[2]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[8]
Mitchell syndrome	DIS1O9CZ	Strong	Autosomal dominant	[1]
Mitochondrial disease	DISKAHA3	Strong	Altered Expression	[9]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[10]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Stroke	DISX6UHX	Strong	Biomarker	[5]
Leukodystrophy	DISVY1TT	moderate	Biomarker	[11]
Lipid metabolism disorder	DISEOA7S	moderate	Altered Expression	[12]
Neoplasm	DISZKGEW	Disputed	Biomarker	[13]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[7]
Liver cancer	DISDE4BI	Limited	Altered Expression	[7]
Peroxisomal disorder	DISV185U	Limited	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) increases the Renal failure acute ADR of Cisplatin.	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[33]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[35]

29 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 1 (ACOX1).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[19]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[20]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[22]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[23]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[24]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[25]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[26]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[27]
Allopurinol	DMLPAOB	Approved	Allopurinol increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[28]
Ciprofibrate	DMGC5DB	Approved	Ciprofibrate increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[29]
Sodium acetate anhydrous	DMH21E0	Approved	Sodium acetate anhydrous increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[30]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[31]
CS-038	DM67P0F	Phase 3	CS-038 increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[34]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[31]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[37]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[30]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[25]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[38]
Chlorphrifos oxon	DMGBT68	Investigative	Chlorphrifos oxon affects the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[39]
Raffinose	DMVHDOS	Investigative	Raffinose increases the expression of Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).	[40]

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