General Information of Drug Therapeutic Target (DTT) (ID: TTKWFB8)

DTT Name Catechol-O-methyl-transferase (COMT)
Synonyms S-COMT; MB-COMT; Catechol-O-methyltransferase; COMT
Gene Name COMT
DTT Type
Successful target
[1]
BioChemical Class
Methyltransferase
UniProt ID
COMT_HUMAN
TTD ID
T76904
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.1.1.6
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.
KEGG Pathway
Steroid hormone biosynthesis (hsa00140 )
Tyrosine metabolism (hsa00350 )
Metabolic pathways (hsa01100 )
Dopaminergic synapse (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-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
3 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Entacapone DMLBVKQ Parkinson disease 8A00.0 Approved [2]
Opicapone DM1BKA6 Parkinson disease 8A00.0 Approved [3]
Tolcapone DM8MNVO Parkinson disease 8A00.0 Approved [1]
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2 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
BIA 3-202 DMG3ON2 Parkinson disease 8A00.0 Phase 2 [4]
CGP-28014 DMYNTQV Major depressive disorder 6A70.3 Phase 2 [5]
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1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Nitecapone DMSJYEX Pain MG30-MG3Z Discontinued in Phase 2 [6]
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1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PGX-200097 DM1A2UI Schizophrenia 6A20 Preclinical [7]
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8 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(3,4-DIHYDROXY-2-NITROPHENYL)(PHENYL)METHANONE DMTB41W Discovery agent N.A. Investigative [8]
1-(3,4-dihydroxy-2-nitrophenyl)-2-phenylethanone DM9M5D1 Discovery agent N.A. Investigative [9]
1-(3,4-dihydroxy-5-nitrophenyl)-2-phenoxyethanone DMKI719 Discovery agent N.A. Investigative [10]
3,5-Dinitrocatechol DMBGSHD Discovery agent N.A. Investigative [11]
5,6-dihydroxy-7-nitro-2,3-dihydroinden-1-one DM94V8D Discovery agent N.A. Investigative [9]
6,7-dihydroxy-8-nitro-1-tetralone DM9JLUS Discovery agent N.A. Investigative [9]
7,8-dihydroxy-4-phenyl-2H-chromen-2-one DMUB5E8 Discovery agent N.A. Investigative [8]
BIA DM4RZ9A Non-insulin dependent diabetes 5A11 Investigative [8]
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⏷ Show the Full List of 8 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Major depressive disorder 6A20 Pre-frontal cortex 4.34E-01 -0.08 -0.53
Parkinson's disease 8A00.0 Substantia nigra tissue 9.24E-02 0.17 1.09
Schizophrenia 6A20 Pre-frontal cortex 1.82E-01 0.03 0.11
Schizophrenia 6A20 Superior temporal cortex 1.25E-01 -0.04 -0.29
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References

1 Catechol-O-methyltransferase inhibitors in the management of Parkinson's disease. Semin Neurol. 2001;21(1):15-22.
2 Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
4 Chemical synthesis and characterization of conjugates of a novel catechol-O-methyltransferase inhibitor. Bioconjug Chem. 2002 Sep-Oct;13(5):1112-8.
5 CGP 28014, a new inhibitor of cerebral catechol-O-methylation with a non-catechol structure. Naunyn Schmiedebergs Arch Pharmacol. 1990 Sep;342(3):305-11.
6 Effect 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.
7 Schizophrenia, "just the facts" 5. Treatment and prevention. Past, present, and future. Schizophr Res. 2010 Sep;122(1-3):1-23.
8 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
9 Synthesis and biological evaluation of a novel series of "ortho-nitrated" inhibitors of catechol-O-methyltransferase. J Med Chem. 2005 Dec 15;48(25):8070-8.
10 Synthesis, biological evaluation, and molecular modeling studies of a novel, peripherally selective inhibitor of catechol-O-methyltransferase. J Med Chem. 2004 Dec 2;47(25):6207-17.
11 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.