Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDO6HBG)

• DOT Name: Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB)
• Synonyms: SBCAD; EC 1.3.8.5; 2-methyl branched chain acyl-CoA dehydrogenase; 2-MEBCAD; 2-methylbutyryl-coenzyme A dehydrogenase; 2-methylbutyryl-CoA dehydrogenase
• Gene Name: ACADSB
• Related Disease:
  2-methylbutyryl-CoA dehydrogenase deficiency
  Autism
  Breast cancer
  Breast carcinoma
  Essential hypertension
  Hepatocellular carcinoma
  High blood pressure
  Hyperlipidemia
  Type-1/2 diabetes
  3-hydroxy-3-methylglutaryl-CoA synthase deficiency
  3-methylglutaconic aciduria
  Amelocerebrohypohidrotic syndrome
  Ehlers-Danlos syndrome, kyphoscoliotic and deafness type
  HSD10 mitochondrial disease
  Isobutyryl-CoA dehydrogenase deficiency
  Short chain acyl-CoA dehydrogenase deficiency
  Smith-Lemli-Opitz syndrome
• UniProt ID: ACDSB_HUMAN
• PDB ID: 2JIF
• EC Number: 1.3.8.5
• Pfam ID: PF00441 ; PF02770 ; PF02771
• Sequence:
  MEGLAVRLLRGSRLLRRNFLTCLSSWKIPPHVSKSSQSEALLNITNNGIHFAPLQTFTDE
  EMMIKSSVKKFAQEQIAPLVSTMDENSKMEKSVIQGLFQQGLMGIEVDPEYGGTGASFLS
  TVLVIEELAKVDASVAVFCEIQNTLINTLIRKHGTEEQKATYLPQLTTEKVGSFCLSEAG
  AGSDSFALKTRADKEGDYYVLNGSKMWISSAEHAGLFLVMANVDPTIGYKGITSFLVDRD
  TPGLHIGKPENKLGLRASSTCPLTFENVKVPEANILGQIGHGYKYAIGSLNEGRIGIAAQ
  MLGLAQGCFDYTIPYIKERIQFGKRLFDFQGLQHQVAHVATQLEAARLLTYNAARLLEAG
  KPFIKEASMAKYYASEIAGQTTSKCIEWMGGVGYTKDYPVEKYFRDAKIGTIYEGASNIQ
  LNTIAKHIDAEY
• Function: Short and branched chain specific acyl-CoA dehydrogenase that catalyzes the removal of one hydrogen from C-2 and C-3 of the fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA. Among the different mitochondrial acyl-CoA dehydrogenases, acts specifically on short and branched chain acyl-CoA derivatives such as (S)-2-methylbutyryl-CoA as well as short straight chain acyl-CoAs such as butyryl-CoA. Plays an important role in the metabolism of L-isoleucine by catalyzing the dehydrogenation of 2-methylbutyryl-CoA, one of the steps of the L-isoleucine catabolic pathway. Can also act on valproyl-CoA, a metabolite of valproic acid, an antiepileptic drug.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway:
  Fatty acid degradation (hsa00071)
  Valine, leucine and isoleucine degradation (hsa00280)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
• Reactome Pathway: Branched-chain amino acid catabolism (R-HSA-70895)
• BioCyc Pathway: MetaCyc:HS10828-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
2-methylbutyryl-CoA dehydrogenase deficiency	DISVIOPK	Definitive	Autosomal recessive	[1]
Autism	DISV4V1Z	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Essential hypertension	DIS7WI98	Strong	Genetic Variation	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[4]
Hyperlipidemia	DIS61J3S	Strong	Genetic Variation	[4]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[4]
3-hydroxy-3-methylglutaryl-CoA synthase deficiency	DISIIU6G	Limited	Biomarker	[6]
3-methylglutaconic aciduria	DIS8G1WP	Limited	Biomarker	[6]
Amelocerebrohypohidrotic syndrome	DIS0DATV	Limited	Biomarker	[6]
Ehlers-Danlos syndrome, kyphoscoliotic and deafness type	DISA74TB	Limited	Biomarker	[6]
HSD10 mitochondrial disease	DISCJYFW	Limited	Biomarker	[6]
Isobutyryl-CoA dehydrogenase deficiency	DIS9ORX6	Limited	Biomarker	[6]
Short chain acyl-CoA dehydrogenase deficiency	DISDDRPY	Limited	Biomarker	[6]
Smith-Lemli-Opitz syndrome	DISX9ZUA	Limited	Biomarker	[6]

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 Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[21]

15 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 Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[15]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[16]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[18]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[22]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB).	[23]

References

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• [20] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [21] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [22] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
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