Details of Drug Off-Target (DOT)

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

• DOT Name: Catechol O-methyltransferase (COMT)
• Synonyms: EC 2.1.1.6
• Gene Name: COMT
• Related Disease: Paroxysmal dyskinesia
• UniProt ID: COMT_HUMAN
• PDB ID: 3A7E; 3BWM; 3BWY; 4PYI; 4PYJ; 4PYK; 4XUC; 4XUD; 4XUE; 5LSA; 6I3C; 6I3D
• EC Number: 2.1.1.6
• Pfam ID: PF01596
• Sequence:
  MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRIL
  NHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCG
  YSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKY
  DVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFE
  CTHYQSFLEYREVVDGLEKAIYKGPGSEAGP
• Function: Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
• Tissue Specificity: Brain, liver, placenta, lymphocytes and erythrocytes.
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Tyrosine metabolism (hsa00350)
  Metabolic pathways (hsa01100)
  Dopaminergic sy.pse (hsa04728)
• Reactome Pathway:
  Enzymatic degradation of dopamine by COMT (R-HSA-379397)
  Enzymatic degradation of Dopamine by monoamine oxidase (R-HSA-379398)
  Potential therapeutics for SARS (R-HSA-9679191)
  Methylation (R-HSA-156581)
• BioCyc Pathway: MetaCyc:HS01791-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Paroxysmal dyskinesia	DIS5XVXE	Moderate	Autosomal dominant	[1]

This DOT Affected the Drug Response of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Catechol O-methyltransferase (COMT) affects the response to substance of Cisplatin.	[25]
Marinol	DM70IK5	Approved	Catechol O-methyltransferase (COMT) increases the response to substance of Marinol.	[26]
Clozapine	DMFC71L	Approved	Catechol O-methyltransferase (COMT) increases the response to substance of Clozapine.	[27]
Methamphetamine	DMPM4SK	Approved	Catechol O-methyltransferase (COMT) increases the response to substance of Methamphetamine.	[28]
Dextroamphetamine	DMMIHVP	Approved	Catechol O-methyltransferase (COMT) affects the response to substance of Dextroamphetamine.	[31]
Modafinil	DMYILBE	Approved	Catechol O-methyltransferase (COMT) affects the response to substance of Modafinil.	[32]
Catechol	DML0YEK	Investigative	Catechol O-methyltransferase (COMT) increases the response to substance of Catechol.	[34]

This DOT Affected the Biotransformations of 19 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estrone	DM5T6US	Approved	Catechol O-methyltransferase (COMT) increases the methylation of Estrone.	[29]
Dopamine	DMPGUCF	Approved	Catechol O-methyltransferase (COMT) increases the methylation of Dopamine.	[30]
Isoproterenol	DMK7MEY	Approved	Catechol O-methyltransferase (COMT) increases the methylation of Isoproterenol.	[30]
Epinephrine	DM3KJBC	Approved	Catechol O-methyltransferase (COMT) increases the methylation of Epinephrine.	[30]
Norepinephrine	DMOUC09	Approved	Catechol O-methyltransferase (COMT) increases the methylation of Norepinephrine.	[30]
Dobutamine	DMD1B8Z	Approved	Catechol O-methyltransferase (COMT) increases the methylation of Dobutamine.	[30]
Levodopa	DMN3E57	Approved	Catechol O-methyltransferase (COMT) increases the methylation of Levodopa.	[30]
Methyldopa	DM5I621	Approved	Catechol O-methyltransferase (COMT) increases the methylation of Methyldopa.	[30]
Carbidopa	DMHRG8Q	Approved	Catechol O-methyltransferase (COMT) increases the methylation of Carbidopa.	[30]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	Catechol O-methyltransferase (COMT) increases the methylation of 3,4-Dihydroxycinnamic Acid.	[30]
Benserazide	DMLU8NX	Phase 3	Catechol O-methyltransferase (COMT) increases the methylation of Benserazide.	[30]
Dihydrexidine	DMACPQO	Phase 1/2	Catechol O-methyltransferase (COMT) increases the methylation of Dihydrexidine.	[30]
Steroid derivative 1	DMB0NVQ	Patented	Catechol O-methyltransferase (COMT) affects the chemical synthesis of Steroid derivative 1.	[33]
SKF 38393	DMIMJ8Z	Terminated	Catechol O-methyltransferase (COMT) increases the methylation of SKF 38393.	[30]
Hydroxyestradiol	DMJXQME	Investigative	Catechol O-methyltransferase (COMT) increases the methylation of Hydroxyestradiol.	[13]
2-hydroxy-17beta-estradiol	DMM9Z0B	Investigative	Catechol O-methyltransferase (COMT) increases the methylation of 2-hydroxy-17beta-estradiol.	[30]
Pyrogallol	DMG5KDY	Investigative	Catechol O-methyltransferase (COMT) increases the methylation of Pyrogallol.	[30]
Metanephrine	DMTGMB1	Investigative	Catechol O-methyltransferase (COMT) increases the chemical synthesis of Metanephrine.	[35]
2-(3,4-Dihydroxyphenyl)Acetic Acid	DMSZ0H9	Investigative	Catechol O-methyltransferase (COMT) increases the methylation of 2-(3,4-Dihydroxyphenyl)Acetic Acid.	[30]

2 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 Catechol O-methyltransferase (COMT).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Catechol O-methyltransferase (COMT).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Catechol O-methyltransferase (COMT).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Catechol O-methyltransferase (COMT).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Catechol O-methyltransferase (COMT).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Catechol O-methyltransferase (COMT).	[6]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Catechol O-methyltransferase (COMT).	[7]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Catechol O-methyltransferase (COMT).	[8]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Catechol O-methyltransferase (COMT).	[9]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide increases the expression of Catechol O-methyltransferase (COMT).	[10]
Tolcapone	DM8MNVO	Approved	Tolcapone decreases the activity of Catechol O-methyltransferase (COMT).	[11]
Entacapone	DMLBVKQ	Approved	Entacapone decreases the activity of Catechol O-methyltransferase (COMT).	[12]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Catechol O-methyltransferase (COMT).	[13]
GSK618334	DMJPXZ4	Phase 1	GSK618334 increases the expression of Catechol O-methyltransferase (COMT).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Catechol O-methyltransferase (COMT).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Catechol O-methyltransferase (COMT).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Catechol O-methyltransferase (COMT).	[18]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Catechol O-methyltransferase (COMT).	[19]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Catechol O-methyltransferase (COMT).	[20]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Catechol O-methyltransferase (COMT).	[6]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Catechol O-methyltransferase (COMT).	[21]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Catechol O-methyltransferase (COMT).	[22]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate decreases the expression of Catechol O-methyltransferase (COMT).	[23]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid affects the expression of Catechol O-methyltransferase (COMT).	[24]
Daidzein	DMRFTJX	Investigative	Daidzein decreases the expression of Catechol O-methyltransferase (COMT).	[13]

References

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