Target Information

Target General Infomation
Target ID
T76904
Former ID
TTDS00362
Target Name
Catechol-O-methyl-transferase
Gene Name
COMT
Synonyms
Catechol-O-methyltransferase; MB-COMT; S-COMT; COMT
Target Type
Successful
Disease Major depressive disorder [ICD9: 296.2, 296.3, 710.0; ICD10: F32, F33, M32]
Non-insulin dependent diabetes [ICD10: E11.9]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Parkinson's disease [ICD9: 332; ICD10: G20]
Parkinson's disease; Restless legs syndrome [ICD9: 332, 333.94; ICD10: F02.3, G20, G25.8]
Schizophrenia [ICD9: 295; ICD10: F20]
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.
BioChemical Class
Methyltransferase superfamily
Target Validation
T76904
UniProt ID
P21964
EC Number
EC 2.1.1.6
Sequence
MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRIL
NHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCG
YSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKY
DVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFE
CTHYQSFLEYREVVDGLEKAIYKGPGSEAGP
Drugs and Mode of Action
Drug(s) Entacapone Drug Info Approved Parkinson's disease [536923], [541757]
Tolcapone Drug Info Approved Parkinson's disease [536923], [541756]
Entacapone+levodopa+carbidopa Drug Info Phase 3 Parkinson's disease; Restless legs syndrome [544058]
Opicapone Drug Info Phase 3 Parkinson's disease [532159]
BIA 3-202 Drug Info Phase 2 Parkinson's disease [529342]
CGP-28014 Drug Info Phase 2 Major depressive disorder [530430]
PGX-200097 Drug Info Preclinical Schizophrenia [548315]
Nitecapone Drug Info Discontinued in Phase 2 Pain [544833]
Inhibitor (3,4-DIHYDROXY-2-NITROPHENYL)(PHENYL)METHANONE Drug Info [551374]
1-(3,4-dihydroxy-2-nitrophenyl)-2-phenylethanone Drug Info [527918]
1-(3,4-dihydroxy-5-nitrophenyl)-2-phenoxyethanone Drug Info [527307]
3,5-Dinitrocatechol Drug Info [551393]
5,6-dihydroxy-7-nitro-2,3-dihydroinden-1-one Drug Info [527918]
6,7-dihydroxy-8-nitro-1-tetralone Drug Info [527918]
7,8-dihydroxy-4-phenyl-2H-chromen-2-one Drug Info [551374]
BIA Drug Info [551374]
BIA 3-202 Drug Info [535563]
Entacapone Drug Info [535173], [535204]
Entacapone+levodopa+carbidopa Drug Info [536121]
Opicapone Drug Info [532159]
PGX-200097 Drug Info [531048]
Tolcapone Drug Info [534927], [535173]
Modulator CGP-28014 Drug Info [530430]
Nitecapone Drug Info [531946]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway L-dopa degradation
Dopamine degradation
Noradrenaline and adrenaline degradation
KEGG Pathway Steroid hormone biosynthesis
Tyrosine metabolism
Metabolic pathways
Dopaminergic synapse
PANTHER Pathway Adrenaline and noradrenaline biosynthesis
Dopamine receptor mediated signaling pathway
PathWhiz Pathway Tyrosine Metabolism
WikiPathways Methylation Pathways
Metapathway biotransformation
Estrogen metabolism
Biogenic Amine Synthesis
Dopamine metabolism
Phase II conjugation
Neurotransmitter Clearance In The Synaptic Cleft
References
Ref 529342Effects of nebicapone on levodopa pharmacokinetics, catechol-O-methyltransferase activity, and motor fluctuations in patients with Parkinson disease. Clin Neuropharmacol. 2008 Jan-Feb;31(1):2-18.
Ref 530430CGP 28014, a new inhibitor of cerebral catechol-O-methylation with a non-catechol structure. Naunyn Schmiedebergs Arch Pharmacol. 1990 Sep;342(3):305-11.
Ref 532159Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor. Clin Pharmacokinet. 2013 Feb;52(2):139-51.
Ref 536923Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42.
Ref 541756(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6646).
Ref 541757(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6647).
Ref 544058Optimizing levodopa therapy for Parkinson's disease with levodopa/carbidopa/entacapone: implications from a clinical and patient perspective. Neuropsychiatr Dis Treat. 2008 February; 4(1): 39-47.
Ref 544833Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001267)
Ref 548315Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024498)
Ref 527307J Med Chem. 2004 Dec 2;47(25):6207-17.Synthesis, biological evaluation, and molecular modeling studies of a novel, peripherally selective inhibitor of catechol-O-methyltransferase.
Ref 527918J Med Chem. 2005 Dec 15;48(25):8070-8.Synthesis and biological evaluation of a novel series of "ortho-nitrated" inhibitors of catechol-O-methyltransferase.
Ref 530430CGP 28014, a new inhibitor of cerebral catechol-O-methylation with a non-catechol structure. Naunyn Schmiedebergs Arch Pharmacol. 1990 Sep;342(3):305-11.
Ref 531048Schizophrenia, "just the facts" 5. Treatment and prevention. Past, present, and future. Schizophr Res. 2010 Sep;122(1-3):1-23.
Ref 531946Effect of a novel catechol-O-methyltransferase inhibitor, nitecapone, on the metabolism of L-dopa in healthy volunteers. Clin Neuropharmacol. 1990 Oct;13(5):436-47.
Ref 532159Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor. Clin Pharmacokinet. 2013 Feb;52(2):139-51.
Ref 534927Tolcapone: a novel approach to Parkinson's disease. Am J Health Syst Pharm. 1999 Nov 1;56(21):2195-205.
Ref 535173Catechol-O-methyltransferase inhibitors in the management of Parkinson's disease. Semin Neurol. 2001;21(1):15-22.
Ref 535204Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771.
Ref 535563Chemical synthesis and characterization of conjugates of a novel catechol-O-methyltransferase inhibitor. Bioconjug Chem. 2002 Sep-Oct;13(5):1112-8.
Ref 536121Emerging drugs for restless legs syndrome. Expert Opin Emerg Drugs. 2005 Aug;10(3):537-52.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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