Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJDOL20)

• DOT Name: Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH)
• Synonyms: HCDH; EC 1.1.1.35; Medium and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase; Short-chain 3-hydroxyacyl-CoA dehydrogenase
• Gene Name: HADH
• Related Disease:
  3-hydroxyacyl-CoA dehydrogenase deficiency
  Metabolic disorder
  Obsolete hyperinsulinism due to short chain 3-hydroxylacyl-CoA dehydrogenase deficiency
  Cardiac failure
  Congestive heart failure
  Hyperinsulinemic hypoglycemia, familial, 4
  Hypoglycemia
  Mitochondrial trifunctional protein deficiency
  Non-alcoholic fatty liver disease
  Obesity
  Peroxisomal disorder
  Adrenoleukodystrophy
  Hyperinsulinemia
  Advanced cancer
  Laryngeal carcinoma
  Myocardial infarction
  Non-insulin dependent diabetes
  Precancerous condition
• UniProt ID: HCDH_HUMAN
• PDB ID: 1F0Y; 1F12; 1F14; 1F17; 1IL0; 1LSJ; 1LSO; 1M75; 1M76; 2HDH; 3HAD; 3RQS
• EC Number: 1.1.1.35
• Pfam ID: PF00725 ; PF02737
• Sequence:
  MAFVTRQFMRSVSSSSTASASAKKIIVKHVTVIGGGLMGAGIAQVAAATGHTVVLVDQTE
  DILAKSKKGIEESLRKVAKKKFAENLKAGDEFVEKTLSTIATSTDAASVVHSTDLVVEAI
  VENLKVKNELFKRLDKFAAEHTIFASNTSSLQITSIANATTRQDRFAGLHFFNPVPVMKL
  VEVIKTPMTSQKTFESLVDFSKALGKHPVSCKDTPGFIVNRLLVPYLMEAIRLYERGDAS
  KEDIDTAMKLGAGYPMGPFELLDYVGLDTTKFIVDGWHEMDAENPLHQPSPSLNKLVAEN
  KFGKKTGEGFYKYK
• Function: Mitochondrial fatty acid beta-oxidation enzyme that catalyzes the third step of the beta-oxidation cycle for medium and short-chain 3-hydroxy fatty acyl-CoAs (C4 to C10). Plays a role in the control of insulin secretion by inhibiting the activation of glutamate dehydrogenase 1 (GLUD1), an enzyme that has an important role in regulating amino acid-induced insulin secretion.
• Tissue Specificity: Expressed in liver, kidney, pancreas, heart and skeletal muscle.
• KEGG Pathway:
  Fatty acid elongation (hsa00062)
  Fatty acid degradation (hsa00071)
  Valine, leucine and isoleucine degradation (hsa00280)
  Lysine degradation (hsa00310)
  Tryptophan metabolism (hsa00380)
  Butanoate metabolism (hsa00650)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
• Reactome Pathway:
  Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA (R-HSA-77346)
  Beta oxidation of octanoyl-CoA to hexanoyl-CoA (R-HSA-77348)
  Beta oxidation of hexanoyl-CoA to butanoyl-CoA (R-HSA-77350)
  Beta oxidation of butanoyl-CoA to acetyl-CoA (R-HSA-77352)
  Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA (R-HSA-77310)
• BioCyc Pathway: MetaCyc:HS06563-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
3-hydroxyacyl-CoA dehydrogenase deficiency	DISBJ31P	Definitive	Autosomal recessive	[1]
Metabolic disorder	DIS71G5H	Definitive	Genetic Variation	[2]
Obsolete hyperinsulinism due to short chain 3-hydroxylacyl-CoA dehydrogenase deficiency	DISC55HT	Definitive	Autosomal recessive	[3]
Cardiac failure	DISDC067	Strong	Altered Expression	[4]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[4]
Hyperinsulinemic hypoglycemia, familial, 4	DIS8A8YY	Strong	Autosomal recessive	[5]
Hypoglycemia	DISRCKR7	Strong	Genetic Variation	[6]
Mitochondrial trifunctional protein deficiency	DIS2MYYR	Strong	Genetic Variation	[7]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[8]
Obesity	DIS47Y1K	Strong	Biomarker	[9]
Peroxisomal disorder	DISV185U	Strong	Genetic Variation	[10]
Adrenoleukodystrophy	DISTUD1F	moderate	Genetic Variation	[11]
Hyperinsulinemia	DISIDWT6	moderate	Genetic Variation	[12]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[13]
Laryngeal carcinoma	DISNHCIV	Limited	Genetic Variation	[13]
Myocardial infarction	DIS655KI	Limited	Biomarker	[14]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[15]
Precancerous condition	DISV06FL	Limited	Biomarker	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH) affects the response to substance of Topotecan.	[40]
Vinblastine	DM5TVS3	Approved	Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH) affects the response to substance of Vinblastine.	[40]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
2-Propanol, Isopropanol	DML5O0H	Investigative	Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH) increases the metabolism of 2-Propanol, Isopropanol.	[41]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	Investigative	Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH) increases the metabolism of Nicotinamide-Adenine-Dinucleotide.	[41]

24 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[22]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[23]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[24]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[25]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[26]
Marinol	DM70IK5	Approved	Marinol increases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[27]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[28]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[29]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[30]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[31]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[32]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[33]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[34]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[36]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[38]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH).	[39]

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