Discovery of a novel chemotype of tyrosine kinase inhibitors by fragment-based docking and molecular dynamics

ACS Medicinal Chemistry Letters

Volumn 3, Issue 10, 2012, Pages 834-838

  Zhao, Hongtao ^a   Dong, Jing ^a   Lafleur, Karine ^a   Nevado, Cristina ^a   Caflisch, Amedeo ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

angiogenesis; cancer; EphB4 kinase; explicit solvent MD; In silico screening

Indexed keywords

EPHRIN RECEPTOR B4; HYDROXYL GROUP;

ARTICLE; CRYSTAL STRUCTURE; ENZYMATIC ASSAY; ENZYME ACTIVE SITE; HYDROGEN BOND; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR WEIGHT; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

EID: 84867352362     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml3001984     Document Type: Article

References (26)

1. Noberini, R.; Lamberto, I.; Pasquale, E. B. Targeting Eph receptors with peptides and small molecules: progress and challenges Semin. Cell Dev. Biol. 2012, 23, 51-7
2. Tognolini, M.; Incerti, M.; Hassan-Mohamed, I.; Giorgio, C.; Russo, S.; Bruni, R.; Lelli, B.; Bracci, L.; Noberini, R.; Pasquale, E. B.; Barocelli, E.; Vicini, P.; Mor, M.; Lodola, A. Structure-activity relationships and mechanism of action of Eph-ephrin antagonists: interaction of cholanic acid with the EphA2 receptor ChemMedChem 2012, 7, 1071-83
3. Wang, S.; Placzek, W. J.; Stebbins, J. L.; Mitra, S.; Noberini, R.; Koolpe, M.; Zhang, Z.; Dahl, R.; Pasquale, E. B.; Pellecchia, M. Novel targeted system to deliver chemotherapeutic drugs to EphA2-expressing cancer cells J. Med. Chem. 2012, 55, 2427-36
4. Miyazaki, Y.; Nakano, M.; Sato, H.; Truesdale, A. T.; Stuart, J. D.; Nartey, E. N.; Hightower, K. E.; Kane-Carson, L. Design and effective synthesis of novel templates, 3,7-diphenyl-4-amino-thieno and furo-[3,2-c]pyridines as protein kinase inhibitors and in vitro evaluation targeting angiogenetic kinases Bioorg. Med. Chem. Lett. 2007, 17, 250-4
5. Bardelle, C.; Cross, D.; Davenport, S.; Kettle, J. G.; Ko, E. J.; Leach, A. G.; Mortlock, A.; Read, J.; Roberts, N. J.; Robins, P.; Williams, E. J. Inhibitors of the tyrosine kinase EphB4. Part 1: Structure-based design and optimization of a series of 2,4-bis-anilinopyrimidines Bioorg. Med. Chem. Lett. 2008, 18, 2776-80
6. Sun, L.; Liang, C.; Shirazian, S.; Zhou, Y.; Miller, T.; Cui, J.; Fukuda, J. Y.; Chu, J. Y.; Nematalla, A.; Wang, X.; Chen, H.; Sistla, A.; Luu, T. C.; Tang, F.; Wei, J.; Tang, C. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase J. Med. Chem. 2003, 46, 1116-9
7. Lafleur, K.; Huang, D.; Zhou, T.; Caflisch, A.; Nevado, C. Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4) J. Med. Chem. 2009, 52, 6433-46
8. Zhao, H.; Huang, D. Hydrogen bonding penalty upon ligand binding PLoS One 2011, 6, e19923
9. van Linden, O. P.; Farenc, C.; Zoutman, W. H.; Hameetman, L.; Wijtmans, M.; Leurs, R.; Tensen, C. P.; Siegal, G.; de Esch, I. J. Fragment based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase Eur. J. Med. Chem. 2012, 47, 493-500
10. Choi, Y.; Syeda, F.; Walker, J. R.; Finerty, P. J., Jr.; Cuerrier, D.; Wojciechowski, A.; Liu, Q.; Dhe-Paganon, S.; Gray, N. S. Discovery and structural analysis of Eph receptor tyrosine kinase inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 4467-70
11. Martiny-Baron, G.; Holzer, P.; Billy, E.; Schnell, C.; Brueggen, J.; Ferretti, M.; Schmiedeberg, N.; Wood, J. M.; Furet, P.; Imbach, P. The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis Angiogenesis 2010, 13, 259-67
12. Zhao, H.; Huang, D.; Caflisch, A. Discovery of tyrosine kinase inhibitors by docking into an inactive kinase conformation generated by molecular dynamics ChemMedChem 2012, 10.1002/cmdc.201200331
13. Li, G.; Ji, X. D.; Gao, H.; Zhao, J. S.; Xu, J. F.; Sun, Z. J.; Deng, Y. Z.; Shi, S.; Feng, Y. X.; Zhu, Y. Q.; Wang, T.; Li, J. J.; Xie, D. EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex Nat. Commun. 2012, 3, 667
14. Kolb, P.; Kipouros, C. B.; Huang, D.; Caflisch, A. Structure-based tailoring of compound libraries for high-throughput screening: discovery of novel EphB4 kinase inhibitors Proteins 2008, 73, 11-8
15. Irwin, J. J.; Shoichet, B. K. ZINC - a free database of commercially available compounds for virtual screening J. Chem. Inf. Model. 2005, 45, 177-82
16. Congreve, M.; Chessari, G.; Tisi, D.; Woodhead, A. J. Recent developments in fragment-based drug discovery J. Med. Chem. 2008, 51, 3661-80
17. Roughley, S. D.; Hubbard, R. E. How well can fragments explore accessed chemical space? A case study from heat shock protein 90 J. Med. Chem. 2011, 54, 3989-4005
18. Kolb, P.; Caflisch, A. Automatic and efficient decomposition of two-dimensional structures of small molecules for fragment-based high-throughput docking J. Med. Chem. 2006, 49, 7384-92
19. Goodsell, D. S.; Olson, A. J. Automated docking of substrates to proteins by simulated annealing Proteins 1990, 8, 195-202
20. Brooks, B. R.; Brooks, C. L., 3rd; Mackerell, A. D., Jr.; Nilsson, L.; Petrella, R. J.; Roux, B.; Won, Y.; Archontis, G.; Bartels, C.; Boresch, S.; Caflisch, A.; Caves, L.; Cui, Q.; Dinner, A. R.; Feig, M.; Fischer, S.; Gao, J.; Hodoscek, M.; Im, W.; Kuczera, K.; Lazaridis, T.; Ma, J.; Ovchinnikov, V.; Paci, E.; Pastor, R. W.; Post, C. B.; Pu, J. Z.; Schaefer, M.; Tidor, B.; Venable, R. M.; Woodcock, H. L.; Wu, X.; Yang, W.; York, D. M.; Karplus, M. CHARMM: the biomolecular simulation program J. Comput. Chem. 2009, 30, 1545-614
21. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of Simple Potential Functions for Simulating Liquid Water J. Chem. Phys. 1983, 79, 926-935
22. Zuccotto, F.; Ardini, E.; Casale, E.; Angiolini, M. Through the "gatekeeper door": exploiting the active kinase conformation J. Med. Chem. 2010, 53, 2681-94
23. Sato, M.; Ogasawara, H.; Oi, K.; Kato, T. Synthesis of 1,3-Dioxin-4-One Derivatives Chem. Pharm. Bull. 1983, 31, 1896-1901
24. Miriyala, B.; Williamson, J. S. An efficient and rapid synthesis of beta-carboxamide derivatives using 2,2-dimethyl-2H,4H-1,3-dioxin-4-ones by microwave irradiation Tetrahedron Lett. 2003, 44, 7957-7959
25. Bogdanowiczszwed, K.; Policht, A. The Reaction of Malononitrile with Enamines of Some Cyclic Beta-Keto Acid Anilides and Amidines J. Prakt. Chem. 1984, 326, 721-728
26. Huang, D.; Zhou, T.; Lafleur, K.; Nevado, C.; Caflisch, A. Kinase selectivity potential for inhibitors targeting the ATP binding site: a network analysis Bioinformatics 2010, 26, 198-204