Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT50L4XB)

• DOT Name: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL)
• Synonyms: VLCAD; EC 1.3.8.9
• Gene Name: ACADVL
• Related Disease:
  Very long chain acyl-CoA dehydrogenase deficiency
  Adrenogenital syndrome
  Alpha-1 antitrypsin deficiency
  Alzheimer disease
  Cardiomyopathy
  Complement component 2 deficiency
  Congenital adrenal hyperplasia
  Fatty liver disease
  Hypoglycemia
  Metabolic myopathy
  Mitochondrial trifunctional protein deficiency
  Respiratory failure
  Sensorineural hearing loss disorder
  Von Willebrand disease type 2N
  Adrenal adenoma
  Aplasia cutis congenita
  Corpus callosum, agenesis of
  Hypertrophic cardiomyopathy
  Myopathy
• UniProt ID: ACADV_HUMAN
• PDB ID: 2UXW; 3B96; 7S7G
• EC Number: 1.3.8.9
• Pfam ID: PF21343 ; PF00441 ; PF02770 ; PF02771
• Sequence:
  MQAARMAASLGRQLLRLGGGSSRLTALLGQPRPGPARRPYAGGAAQLALDKSDSHPSDAL
  TRKKPAKAESKSFAVGMFKGQLTTDQVFPYPSVLNEEQTQFLKELVEPVSRFFEEVNDPA
  KNDALEMVEETTWQGLKELGAFGLQVPSELGGVGLCNTQYARLVEIVGMHDLGVGITLGA
  HQSIGFKGILLFGTKAQKEKYLPKLASGETVAAFCLTEPSSGSDAASIRTSAVPSPCGKY
  YTLNGSKLWISNGGLADIFTVFAKTPVTDPATGAVKEKITAFVVERGFGGITHGPPEKKM
  GIKASNTAEVFFDGVRVPSENVLGEVGSGFKVAMHILNNGRFGMAAALAGTMRGIIAKAV
  DHATNRTQFGEKIHNFGLIQEKLARMVMLQYVTESMAYMVSANMDQGATDFQIEAAISKI
  FGSEAAWKVTDECIQIMGGMGFMKEPGVERVLRDLRIFRIFEGTNDILRLFVALQGCMDK
  GKELSGLGSALKNPFGNAGLLLGEAGKQLRRRAGLGSGLSLSGLVHPELSRSGELAVRAL
  EQFATVVEAKLIKHKKGIVNEQFLLQRLADGAIDLYAMVVVLSRASRSLSEGHPTAQHEK
  MLCDTWCIEAAARIREGMAALQSDPWQQELYRNFKSISKALVERGGVVTSNPLGF
• Function: Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats. The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA. Among the different mitochondrial acyl-CoA dehydrogenases, very long-chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with saturated 12 to 24 carbons long primary chains.
• Tissue Specificity: Predominantly expressed in heart and skeletal muscle (at protein level). Also detected in kidney and liver (at protein level).
• KEGG Pathway:
  Fatty acid degradation (hsa00071)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  Beta oxidation of palmitoyl-CoA to myristoyl-CoA (R-HSA-77305)
  XBP1(S) activates chaperone genes (R-HSA-381038)
• BioCyc Pathway: MetaCyc:ENSG00000072778-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Very long chain acyl-CoA dehydrogenase deficiency	DISB7TEQ	Definitive	Autosomal recessive	[1]
Adrenogenital syndrome	DIS2N76U	Strong	Genetic Variation	[2]
Alpha-1 antitrypsin deficiency	DISQKEHW	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[4]
Complement component 2 deficiency	DIS8OWGU	Strong	Genetic Variation	[2]
Congenital adrenal hyperplasia	DISG873W	Strong	Genetic Variation	[2]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[5]
Hypoglycemia	DISRCKR7	Strong	Genetic Variation	[4]
Metabolic myopathy	DISSE3BW	Strong	Biomarker	[6]
Mitochondrial trifunctional protein deficiency	DIS2MYYR	Strong	Altered Expression	[7]
Respiratory failure	DISVMYJO	Strong	Genetic Variation	[8]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[2]
Von Willebrand disease type 2N	DIS7S2QL	Strong	Genetic Variation	[2]
Adrenal adenoma	DISC2UN8	Limited	Genetic Variation	[9]
Aplasia cutis congenita	DISMDAYM	Limited	Altered Expression	[9]
Corpus callosum, agenesis of	DISO9P40	Limited	Altered Expression	[9]
Hypertrophic cardiomyopathy	DISQG2AI	Limited	Genetic Variation	[10]
Myopathy	DISOWG27	Limited	Genetic Variation	[4]

21 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 Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[16]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[17]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[19]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[20]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[21]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[22]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[20]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[23]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[24]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[26]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[27]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[29]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[30]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone decreases the expression of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[31]

1 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 decreases the methylation of Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL).	[25]

References

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