Fragment shuffling: An automated workflow for three-dimensional fragment-based ligand design

Journal of Chemical Information and Modeling

Volumn 49, Issue 5, 2009, Pages 1211-1222

  Nisius, Britta ^a,c   Rester, Ulrich ^a,b  

^a BAYER PHARMA AG   (Germany)

^b BAYER AG   (Germany)

^c UNIVERSITY OF BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYMES; LEAD COMPOUNDS; LIGANDS;

AUTOMATED WORKFLOW; GREEDY SEARCH ALGORITHMS; INCREMENTAL CONSTRUCTION; INDIVIDUAL SCORES; LEAD IDENTIFICATION; LIGAND STRUCTURE; PROSPECTIVE STUDY; THROMBIN INHIBITORS;

DESIGN;

LIGAND;

ARTICLE; CHEMICAL STRUCTURE; DRUG DESIGN; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; LIGANDS; MODELS, MOLECULAR;

EID: 66249100884     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci8004572     Document Type: Article

References (49)

1. Chemogenomics in drug discovery; Kubinyi, H., Muller, G., Eds.; Wiley-VCH: Weinheim, Germany, 2004.
2. Bernstein, F. C.; Koetzle, T. F.; Williams, G. J. B.; Meyer, E. F.; Brice, M. D.; Rodgers, J. R.; Kennard, O. The Protein Data Bank: A computer-based archival file for macromolecular structures. Eur. J. Biochem. 1977, 80, 319-324.
3. Blundell, T. L.; Jhoti, H.; Abell, C. High-throughput crystallography for lead discovery in drug design. Nat. Rev. Drug Discovery 2002, 1, 45-54.
4. Rees, D. C.; Congreve, M.; Murray, C. W.; Carr, R. Fragment-based lead discovery. Nat. Rev. Drug Discovery 2004, 3, 600-672.
5. Erlanson, D. A.; McDowell, R. S.; O'Brien, T. Fragment-based drug discovery. J. Med. Chem. 2004, 47, 3463-3482.
6. Fragment-based approaches in drug discovery; Jahnke, W., Erlanson, W. A., Eds.; Wiley-VCH: Weinheim, Germany, 2006.
7. Fragment-based drug discovery; Zartler, E. R., Shapiro, M. J. Eds.; Wiley: Chichester, UK, 2008.
8. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand efficiency: A useful metric for lead selection. Drug Discovery Today 2004, 9, 430-431.
9. Alex, A.; Flocco, M. Fragment-based drug discovery: What has it achieved so far. Curr. Top. Med. Chem. 2007, 7, 1544-1567.
10. Pierce, A. C.; Rao, G.; Bemis, G. W. BREED: Generating novel inhibitors through hybridization of known ligands. Application to CDK2, P38, and HIV Protease. J. Med. Chem. 2004, 47, 2768-2775.
11. Maass, P.; Schulz-Gasch, T.; Stahl, M.; Rarey, M. Recore: A fast and versatile method for scaffold hopping based on small molecule crystal structure conformations. J. Chem. Inf. Model. 2007, 47, 390-399.
12. MED-Hybridise; MEDIT SA, 2 rue du Belvedere, 911200 Palaiseau, France, 2008.
13. Fechner, U.; Schneider, G. Flux (1): A virtual synthesis scheme forfragment-based de novo design. J. Chem. Inf. Model. 2006, 46, 699-707.
14. Fechner, U.; Schneider, G. Flux (2): Comparison of molecular mutation and crossover operators for ligand-based de novo design. J. Chem. Inf. Model. 2007, 47, 656-667.
15. Lewell, X. Q.; Judd, D. B.; Watson, S. P.; Hann, M. M. RECAP-Retrosynthetic Combinatorial Analysis Procedure: A powerful new technique for identifying privileged molecular fragments with useful applications in combinatorial chemistry. J. Chem. Inf. Comput. Sci. 1998, 38, 511-522.
16. Schneider, G.; Fechner, U. Computer-based de novo design of drug like molecules. Nat Rev Drug Discovery 2005, 4, 649-663.
17. Böhm, H. J. The computer program LUDI: a new simple method for the de-novo design of enzyme inhibitors. J. Comput.-Aided Mol. Des. 1992, 6, 61-78.
18. Moon, B. J.; Howe, W. J. Computer-aided design of bioactive molecules: A method for receptor-based de novo design. Proteins 1991, 11, 314-328.
19. Newton, A. C. Protein Kinase C: Structure, function, and regulation. J. Biol. Chem. 1995, 48, 28495-28498.
20. Hanessian, S.; Therrien, E.; Granbergb, K.; Nilssonb, I. Targeting thrombin and factor VIIa: Design, synthesis, and inhibitory activity of functionally relevant indolizidinones. Bioorg. Med. Chem. Lett. 2002, 12, 2907-291.
21. Huntington, J. A. Molecular recognition systems of thrombin. J. Thromb. Haemostasis 2005, 3, 1861-1872.
22. Bode, W. Structure and interaction modes of thrombin. Blood Cells Mol. Dis. 2006, 36, 122-130.
23. Semple, J. E. Design and construction of novel thrombin inhibitors featuring P3-P4 quaternary lactam dipeptide surrogates. Bioorg. Med. Chem. Lett. 1998, 8, 2501-2506.
24. Maestro, version S.O, Schrodinger Inc.: 101 SW Main Street Suite, 1300 Portland, OR 97204, 2008.http://www.schroedinger.com/ (accessed Feb 17, 2009).
25. Wang, Z.; Canagarajah, B. J.; Boehm, J. C.; Kassisa, S.; Cobb, M. H.; Young, P. R.; Abdel-Meguid, S.; Adams, J. L.; Goldsmith, E. J. Structural basis of inhibitor selectivity in MAP kinases. Structure 1998, 6, 1117-1128.
26. Shewchuk, L.; Hassell, A.; Wisely, B.; Rocque, W.; Holmes, W.; Veal, J.; Kuyper, L. F. Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilino-quinazolines bound to cyclin-dependent kinase 2 and p38 kinase. J. Med. Chem. 2000, 3, 133-138.
27. Clare, P. M.; Poorman, R. A.; Kelley, L. C.; Watenpaugh, K. D.; Bannow, C. A.; Leach, K. L. The cyclin-dependent kinases cdk2 and cdk5 act by a random, anticooperative kinetic mechanism. J. Biol. Chem. 2001, 276, 48292-48299.
28. FlexX, version 2.2.O (pre); Biosolve IT GmbH, An der Ziegelei 75, 53757 Sankt Augustin, Germany, 2007.
29. Protein Data Bank, PDB File Format, 2000. http://www.wwpdb.org/ docs.html (accessed Feb 17, 2009).
30. FlexX GUI, version 1.0; Biosolve IT GmbH, An der Ziegelei 75, 53757 Sankt Augustind, Germany, 2007.
31. MDL SDF V2OOO format; Symyx Technologies, Inc., San Ramon, CA, U.S.A., 2005.
32. Banner, D. W.; Hadvary, P. Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors. J. Mol. Biol. 1991, 266, 20085-20093.
33. Java, version 1.6.O2; Sun Microsystems, Inc., 4150 Network Circle, Santa Clara, CA 95054, 2007.
34. Steinbeck, C.; Han, Y.; Kuhn, S.; Horlacher, O.; Luttmann, E.; Willighagen, E. The Chemistry Development Kit (CDK): An open-source java library for chemo and bioinformatics. J. Chem. Inf. Comput. Sci. 2003, 43, 493-500.
35. Chemistry Development Kit CDK, version 1.0.1; 2007. http:// sourceforge.net/projects/cdk/ (accessed Feb 17, 2009).
36. Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. A fast flexible docking method using an incremental construction algorithm. J. Mol. Biol. 1996,261, 470-489.
37. McMartin, C.; Bohacek, R. S. QXP: Powerful, rapid computer algorithms for structure-based drug design. J. Comput.-AidedMol. Des. 1997,11, 333-344.
38. Egeröd, L. Quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase. EP 1488792, 2005 http://www.freepatentsonline.com/ EP1488792A3.html (accessed Feb 17, 2009).
39. Myers, M. R.; Spade, A. P.; Maguire, M. P.; Persons, P. E. Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties. U.S. Patent 5721237, 1998. http://www.patentstorm.us/patents/5721237.html (accessed Feb 17, 2009).
40. Srivastava, S.; Goswami, L. N.; Dikshit, D. K. Progress in the design of low molecular weight thrombin inhibitors. Med. Res. Rev. 2005, 25, 66-92.
41. Selnick, H. G.; Young, M. B.; Nantermet, P. G.; Barrow, J. C.; Williams, P. D.; Lyle, T. A.; Staas, D. D.; Stauffer, K. J.; Sanderson, P. E. Preparation of amino acid benzylamide and 2-pyridylmethylamide derivatives as thrombin inhibitors. WO 02/064559, 2002.http://www.wipo.int/pctdb/en/wo.jsp?wo= 2002064559 (accessed Feb 17, 2009).
42. Lumma, W. C.; Tucker, T. J.; Witherup, K. M.; Brady, S. F., Whitter, W. L.; Vacca, J. P., Coburn, C. Thrombin inhibitors. WO 97/15190, 1997. http://www.freepatentsonline.com/WO1997015190.html (accessed Feb 17, 2009).
43. Tucker, T. J.; Brady, S. F.; Lumma, W. C.; Lewis, S. D.; Gardel, S. J.; Naylor-Olsen, A. M.; Yan, Y.; Sisko, J. T.; Stauffer, K. J.; Lucas, B. Y.; Lynch, J. J.; Cook, J. J.; Stranieri, M. T.; Holahan, M. A.; Lyle, E. A.; Baskin, E. P.; Chen, I.-W.; Dancheck, K. B.; Krueger,J. A.; Cooper, C. M.; Vacca, J. P. Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position. J. Med. Chem. 1998, 41, 3210-3219.
44. Young, M. B.; Barrow, J. C.; Glass, K. L.; Lundell, G. F.; Newton,C. L.; Pellicore, J. M.; Rittle, K. E.; Selnick, H. G.; Stauffer, K. J.; Vacca, J. P.; Williams, P. D.; Bohn, D.; Clayton, F. C.; Cook, J. J.; Krueger, J. A.; Kuo, L. C.; Lewis, S. D.; Lucas, B. J.; McMasters, D. R.; Miller-Stein, C.; Pietrak, B. L. Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors. J. Med. Chem. 2004, 47, 2995-3008.
45. Gillet, V. J.; Myatt, G.; Zsoldos, Z.; Johnson, A. P. SPROUT, HIPPO and CAESA: tools for de novo structure generation and estimation of synthetic accessibility. Perspect. Drug. Discovery Des. 1995, 3, 34-50.
46. Vinkers, H. M.; de Jonge, M. R.; Daevaert, F. F. D.; Heeres, J.; Koymans, L. M. H.; van Lenthe, J. H.; Lewi, P. J.; Timmermann, H.; van Aken, K.; Janssen, P. A. J. SYNOPSIS: SYNthesize and OPtimize System in Silico. J. Med. Chem. 2003, 46, 2765-2773.
47. Baber, J. C.; Feher, M. Predicting synthetic accessibility: application in drug discovery and development. Mini-Rev. Med. Chem. 2004, 4, 681-692.
48. Wunberg, T.; Hendrix, M.; Hillisch, A.; Lobell, M.; Meier, H.; Schmeck, C.; Wild, H.; Hinzen, B. Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits. Drug Discovery Today 2006, 11, 175-180.
49. Lobell, M.; Hendrix, M.; Hinzen, B.; Keldenich, J.; Meier, H.; Schmeck, C.; Schohe-Loop, R.; Wunberg, H.; Hillisch, A. In silico ADMET traffic lights as a tool for the prioritization of HTS hits. ChemMedChem 2006, 1, 1229-1236.