Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA4P0FC)

• DOT Name: Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM)
• Synonyms: MCAD; EC 1.3.8.7; Medium chain acyl-CoA dehydrogenase; MCADH
• Gene Name: ACADM
• Related Disease:
  Medium chain acyl-CoA dehydrogenase deficiency
  Acute liver failure
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Colorectal carcinoma
  Congestive heart failure
  Disorder of glycogen metabolism
  Inherited fatty acid metabolism disorder
  Liver failure
  Long QT syndrome
  Metabolic disorder
  Obesity
  Psoriatic arthritis
  Hypoglycemia
  Inborn error of metabolism
  Clear cell renal carcinoma
  Neuroblastoma
  Phenylketonuria
  Systemic primary carnitine deficiency disease
• UniProt ID: ACADM_HUMAN
• PDB ID: 1EGC; 1EGD; 1EGE; 1T9G; 2A1T; 4P13
• EC Number: 1.3.8.7
• Pfam ID: PF00441 ; PF02770 ; PF02771
• Sequence:
  MAAGFGRCCRVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEI
  IPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQ
  TAIEGNSLGQMPIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKG
  DEYIINGQKMWITNGGKANWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNM
  GQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEAT
  KYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAF
  AGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYK
  N
• Function: Medium-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. Electron transfer flavoprotein (ETF) is the electron acceptor that transfers electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). Among the different mitochondrial acyl-CoA dehydrogenases, medium-chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with saturated 6 to 12 carbons long primary chains.
• KEGG Pathway:
  Fatty acid degradation (hsa00071)
  Valine, leucine and isoleucine degradation (hsa00280)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  PPAR sig.ling pathway (hsa03320)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  mitochondrial fatty acid beta-oxidation of unsaturated fatty acids (R-HSA-77288)
  Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA (R-HSA-77346)
  Beta oxidation of octanoyl-CoA to hexanoyl-CoA (R-HSA-77348)
  PPARA activates gene expression (R-HSA-1989781)
• BioCyc Pathway: MetaCyc:HS04089-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
Medium chain acyl-CoA dehydrogenase deficiency	DISB8C4K	Definitive	Autosomal recessive	[1]
Acute liver failure	DIS5EZKX	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Cardiac failure	DISDC067	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[6]
Disorder of glycogen metabolism	DISYGNOB	Strong	Biomarker	[7]
Inherited fatty acid metabolism disorder	DISOT51Y	Strong	Genetic Variation	[8]
Liver failure	DISLGEL6	Strong	Biomarker	[9]
Long QT syndrome	DISMKWS3	Strong	Biomarker	[10]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[11]
Obesity	DIS47Y1K	Strong	Biomarker	[12]
Psoriatic arthritis	DISLWTG2	Strong	Genetic Variation	[13]
Hypoglycemia	DISRCKR7	moderate	Genetic Variation	[14]
Inborn error of metabolism	DISO5FAY	moderate	Genetic Variation	[15]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[16]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[17]
Phenylketonuria	DISCU56J	Limited	Biomarker	[18]
Systemic primary carnitine deficiency disease	DIS9OPZ4	Limited	Genetic Variation	[19]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM) increases the response to substance of Valproate.	[9]
Etoposide	DMNH3PG	Approved	Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM) affects the response to substance of Etoposide.	[41]

20 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 Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[26]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[27]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[28]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[29]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[30]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[31]
Lindane	DMB8CNL	Approved	Lindane decreases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[32]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[33]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[36]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[37]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[38]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[33]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[39]

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 affects the methylation of Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM).	[35]

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