Target Information
| Target General Information | Top | |||||
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| Target ID |
T76904
(Former ID: TTDS00362)
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| Target Name |
Catechol-O-methyl-transferase (COMT)
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| Synonyms |
S-COMT; MB-COMT; Catechol-O-methyltransferase; COMT
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| Gene Name |
COMT
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Parkinsonism [ICD-11: 8A00] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
Methyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.1.1.6
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| Sequence |
MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRIL
NHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCG YSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKY DVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFE CTHYQSFLEYREVVDGLEKAIYKGPGSEAGP Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A06627 | |||||
| HIT2.0 ID | T03CZ8 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Entacapone | Drug Info | Approved | Parkinson disease | [2], [3] | |
| 2 | Opicapone | Drug Info | Approved | Parkinson disease | [4] | |
| 3 | Tolcapone | Drug Info | Approved | Parkinson disease | [3], [5] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | Entacapone+levodopa+carbidopa | Drug Info | Phase 3 | Restless legs syndrome | [6] | |
| 2 | BIA 3-202 | Drug Info | Phase 2 | Parkinson disease | [7] | |
| 3 | CGP-28014 | Drug Info | Phase 2 | Major depressive disorder | [8] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | Nitecapone | Drug Info | Discontinued in Phase 2 | Pain | [9] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | PGX-200097 | Drug Info | Preclinical | Schizophrenia | [10] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 14 Inhibitor drugs | + | ||||
| 1 | Entacapone | Drug Info | [1], [11] | |||
| 2 | Opicapone | Drug Info | [4] | |||
| 3 | Tolcapone | Drug Info | [1], [12] | |||
| 4 | Entacapone+levodopa+carbidopa | Drug Info | [13] | |||
| 5 | BIA 3-202 | Drug Info | [14] | |||
| 6 | PGX-200097 | Drug Info | [16] | |||
| 7 | (3,4-DIHYDROXY-2-NITROPHENYL)(PHENYL)METHANONE | Drug Info | [17] | |||
| 8 | 1-(3,4-dihydroxy-2-nitrophenyl)-2-phenylethanone | Drug Info | [18] | |||
| 9 | 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenoxyethanone | Drug Info | [19] | |||
| 10 | 3,5-Dinitrocatechol | Drug Info | [20] | |||
| 11 | 5,6-dihydroxy-7-nitro-2,3-dihydroinden-1-one | Drug Info | [18] | |||
| 12 | 6,7-dihydroxy-8-nitro-1-tetralone | Drug Info | [18] | |||
| 13 | 7,8-dihydroxy-4-phenyl-2H-chromen-2-one | Drug Info | [17] | |||
| 14 | BIA | Drug Info | [17] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | CGP-28014 | Drug Info | [8] | |||
| 2 | Nitecapone | Drug Info | [15] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 3 BioCyc Pathways | + | ||||
| 1 | L-dopa degradation | |||||
| 2 | Dopamine degradation | |||||
| 3 | Noradrenaline and adrenaline degradation | |||||
| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Steroid hormone biosynthesis | |||||
| 2 | Tyrosine metabolism | |||||
| 3 | Metabolic pathways | |||||
| 4 | Dopaminergic synapse | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Adrenaline and noradrenaline biosynthesis | |||||
| 2 | Dopamine receptor mediated signaling pathway | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Tyrosine Metabolism | |||||
| WikiPathways | [+] 7 WikiPathways | + | ||||
| 1 | Methylation Pathways | |||||
| 2 | Metapathway biotransformation | |||||
| 3 | Estrogen metabolism | |||||
| 4 | Biogenic Amine Synthesis | |||||
| 5 | Dopamine metabolism | |||||
| 6 | Phase II conjugation | |||||
| 7 | Neurotransmitter Clearance In The Synaptic Cleft | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Catechol-O-methyltransferase inhibitors in the management of Parkinson's disease. Semin Neurol. 2001;21(1):15-22. | |||||
| REF 2 | URL: 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 3 | Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020 | |||||
| REF 5 | URL: 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 6 | Optimizing 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 7 | Effects 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 8 | 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. | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001267) | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024498) | |||||
| REF 11 | Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771. | |||||
| REF 12 | Tolcapone: a novel approach to Parkinson's disease. Am J Health Syst Pharm. 1999 Nov 1;56(21):2195-205. | |||||
| REF 13 | Emerging drugs for restless legs syndrome. Expert Opin Emerg Drugs. 2005 Aug;10(3):537-52. | |||||
| REF 14 | Chemical synthesis and characterization of conjugates of a novel catechol-O-methyltransferase inhibitor. Bioconjug Chem. 2002 Sep-Oct;13(5):1112-8. | |||||
| REF 15 | 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. | |||||
| REF 16 | Schizophrenia, "just the facts" 5. Treatment and prevention. Past, present, and future. Schizophr Res. 2010 Sep;122(1-3):1-23. | |||||
| REF 17 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 18 | 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. | |||||
| REF 19 | 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. | |||||
| REF 20 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
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