A fragment-based approach to identifying S-adenosyl-l-methionine- competitive inhibitors of catechol O-methyl transferase (COMT).

Journal of Medicinal Chemistry

Volumn 57, Issue 12, 2014, Pages 5459-5463

  Lanier, Marion ^a   Ambrus, Geza ^a   Cole, Derek C ^a   Davenport, Richard ^c   Ellery, Jonathan ^c   Fosbeary, Richard ^c   Jennings, Andy J ^a   Kadotani, Akito ^b   Kamada, Yusuke ^b   Kamran, Ruhi ^a   Matsumoto, Shin Ichi ^b   Mizukami, Atsushi ^b   Okubo, Shoichi ^b   Okada, Kengo ^b   Saikatendu, Kumar ^a   Walsh, Louise ^c   Wu, Haihong ^a   Hixon, Mark S ^a  

^a Takeda San Diego Inc   (United States)

^b TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^c Takeda Cambridge Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CATECHOL METHYLTRANSFERASE INHIBITOR; S ADENOSYLMETHIONINE;

ARTICLE; BINDING SITE; COMPLEX FORMATION; CRYSTAL STRUCTURE; LIGAND BINDING;

ANIMALS; BINDING SITES; CATECHOL O-METHYLTRANSFERASE; HUMANS; KINETICS; MICE; MODELS, MOLECULAR; PROTEIN CONFORMATION; PYRAZOLES; RATS; S-ADENOSYLMETHIONINE; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; TRIAZOLES;

EID: 84903514482     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500475k     Document Type: Article

References (27)

1. Copeland, R. A.; Solomon, M. E.; Richon, V. M. Protein methyltransferases as a target class for drug discovery Nature Drug Discovery 2009, 8, 724-732
2. Loenen, W. A. M. S -Adenosylmethionine: jack of all trades and master of everything? Biochem. Soc. Trans. 2006, 34, 330-333
3. Martin, J. L.; McMillan, F. M. SAM (dependent) I AM: the S -adenosylmethionine-dependent methyltransferase fold Curr. Opin. Struct. Biol. 2002, 12, 783-793
4. Miller, D. J.; Ouellette, N.; Evdokimova, E.; Savchenko, A.; Edwards, A.; Anderson, W. F. Crystal complexes of a predicted S -adenosylmethionine- dependent methyltransfe rase reveal a typical AdoMet binding domain and a substrate recognition domain Protein Sci. 2003, 12, 1432-1442
5. Kaakkola, S. Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease Drugs 2000, 59, 1233-1250
6. Bonifácio, M. J.; Palma, P. N.; Almeida, L.; Soares-da-Silva, P. Catechol- O -methyltransferase and its inhibitors in Parkinson's Disease CNS Drug Rev. 2007, 13, 352-379
7. Mannisto, P. T.; Kaakkola, S. Catechol- O -methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors Pharm. Rev. 1999, 51, 593-628
8. Kaakkola, S. Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson's disease Int. Rev. Neurobiol. 2010, 95, 207-225
9. Almeida, L.; Rocha, J. F.; Falcão, A.; Palma, P. N.; Loureiro, A. I.; Pinto, R.; Bonifácio, M. J.; Wright, L. C.; Nunes, T.; Soares-da-Silva, P. Pharmacokinetics, 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, 52, 139-151
10. Borchardt, R. T.; Wu, Y. S. Potential inhibitors of S -adenosylmethionine-dependent methyl transferases. 1. Modification of the amino acid portion of S -adenosylhomocysteine J. Med. Chem. 1974, 17, 862-868
11. Borchardt, R. T.; Huber, J. A.; Wu, Y. S. Potential inhibitors of S -adenosylmethionine-dependent methyltransferases. 2. Modification of the base portion of S -adenosylhomocysteine J. Med. Chem. 1974, 17, 868-873
12. Borchardt, R. T.; Wu, Y. S. Potential inhibitors of S -adenosylmethionine-dependent methyl transferases. 3. Modifications of the sugar portion of S -adenosylhomocysteine J. Med. Chem. 1975, 18, 300-304
13. Borchardt, R. T.; Huber, J. A.; Wu, Y. S. Potential inhibitors of S -adenosylmethionine-dependent methyltransferases. 4. Further modifications of the amino acid and base portions of S -adenosylhomocysteine J. Med. Chem. 1976, 19, 1094-1099
14. Borchardt, R. T.; Wu, Y. S. Potential inhibitors of S -adenosylmethionine-dependent methyl transferases. 6. Structural modifications of S -adenosylhomocysteine J. Med. Chem. 1976, 19, 1104-1110
15. Borchardt, R. T.; Wu, Y. S.; Wu, B. S. Potential inhibitors of S -adenosylmethionine-dependent methyl transferases. 7. Role of the ribosyl moiety in enzymatic binding of S -adenosylhomocysteine J. Med. Chem. 1978, 21, 1307-1310
16. Lerner, C.; Ruf, A.; Gramlich, V.; Masjost, B.; Jakob-Roetne, R.; Borroni, E.; Diederich, F. X-ray crystal structure of a bisubstrate inhibitor bound to the enzyme catechol- O -methyltransferase: a dramatic effect of inhibitor preorganization on binding affinity Angew. Chem., Int. Ed. 2001, 40, 4040-4042
17. Paulini, R.; Trindler, C.; Lerner, C.; Brandli, L.; Schweizer, W. B.; Jakob-Roetne, R.; Zurcher, G.; Borroni, E.; Diederich, F. Bisubstrate inhibitors of catechol O -methyltransferase (COMT): the crucial role of the ribose structural unit for inhibitor binding affinity ChemMedChem 2006, 1, 340-357
18. Ellermann, M.; Paulini, R.; Jakob-Roetne, R.; Lerner, C.; Borroni, E.; Roth, D.; Ehler, A.; Schweizer, W. B.; Schlatter, D.; Rudolph, M. G.; Diederich, F. Molecular recognition at the active site of catechol- O -methyltransferase (COMT): adenine replacements in bisubstrate inhibitors Chem.-Eur. J. 2011, 17, 6369-6381
19. Congreve, M.; Chessari, G.; Tisi, D.; Woodhead, A. J. Recent developments in fragment-based drug discovery J. Med. Chem. 2008, 51, 3661-3680
20. Reynolds, C. H.; Tounge, B. A.; Bembenek, S. D. Ligand binding efficiency: trends, physical basis, and implications J. Med. Chem. 2008, 51, 2432-2438
21. Edwards, M. P.; Price, D. A. Role of physicochemical properties and ligand lipophilicity efficiency in addressing drug safety risks Annu. Rep. Med. Chem. 2010, 45, 381-391
22. Rao, S.; Rossmann, M. Comparison of super-secondary structures in proteins J. Mol. Biol. 1973, 76, 241-256
23. Le Guilloux, V.; Schmidtke, P.; Tuffery, P. F pocket: an open source platform for ligand pocket detection BMC Bioinf. 2009, 10, 168-179 This method identifies pockets in a protein structure and calculates a number of metrics related to the characteristics of each one. A drugability score of 0.5 indicates that binding of druglike molecules is possible, and a value of 1.0 indicates that binding of druglike molecules is very likely.
24. Roughley, S. D.; Hubbard, R. H. How well can fragments explore accessed chemical space? A case study from heat shock protein 90 J. Med. Chem. 2011, 54, 3989-4005
25. Hubbard, R. E.; Davis, B.; Chen, I.; Drysdale, M. J. The SeeDs approach: integrating fragments into drug discovery Curr. Top. Med. Chem. 2007, 7, 1568-1581
26. Coles, M.; Heller, M.; Kessler, H. NMR-based screening technologies Drug Discovery Today 2003, 8, 803-810
27. Fedorov, O.; Niesen, F. H.; Knapp, S. Kinase inhibitor selectivity profiling using differential scanning fluorimetry Methods Mol. Biol. 2012, 795, 109-118