Two 'Golden Ratio' indices in fragment-based drug discovery

Drug Discovery Today

Volumn 14, Issue 5-6, 2009, Pages 321-328

  Orita, Masaya ^a   Ohno, Kazuki ^a   Niimi, Tatsuya ^a  

^a ASTELLAS PHARMA INC   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG INDUSTRY; DRUG RESEARCH; DRUG TARGETING; HIGH THROUGHPUT SCREENING; MATHEMATICAL ANALYSIS; REVIEW;

DRUG DELIVERY SYSTEMS; DRUG DESIGN; DRUG DISCOVERY; HUMANS; LIGANDS; MOLECULAR WEIGHT; SMALL MOLECULE LIBRARIES;

EID: 61649122550     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drudis.2008.10.006     Document Type: Review

References (40)

1. Erlanson D.A., et al. Fragment-based drug discovery. J. Med. Chem. 47 (2004) 3463-3482
2. Alex A.A., and Flocco M.M. Fragment-based drug discovery: what has it achieved so far?. Curr. Topics Med. Chem. 7 (2007) 1544-1567
3. Hajduk P.J., and Greer J. A decade of fragment-based drug design: strategic advances and lessons learned. Nat. Rev. Drug. Discov. 6 (2007) 211-219
4. Congreve M., et al. Recent developments in fragment-based drug discovery. J. Med. Chem. 51 (2008) 3661-3680
5. Albert J.S., et al. An integrated approach to fragment-based lead generation: Philosophy, strategy and case studies from AstraZeneca's drug discovery programmes. Curr. Topics Med. Chem. 7 (2007) 1600-1629
6. Leach A.R., et al. Fragment screening: an introduction. Structure-Based Drug Design (2007), RSC Publishing pp. 142-172
7. Bohacek R.S., et al. The art and practice of structure-based drug design: a molecular modeling perspective. Med. Res. Rev. 16 (1996) 3-50
8. Fink T., et al. Virtual exploration of the small-molecule chemical universe below 160 Daltons. Angewandte Chemie International Edition 44 (2005) 1504-1508
9. Card G.L., et al. A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nat. Biotech. 23 (2005) 201-207
10. Hesterkamp T., et al. Fragment based drug discovery using fluorescence correlation spectroscopy techniques: challenges and solutions. Curr. Top. Med. Chem. 7 (2007) 1582-1591
11. Hann M.M., et al. Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Info. Comp. Sci. 41 (2001) 856-864
12. Boehm H.J., et al. Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guided optimization. A Promising alternative to random screening. J. Med. Chem. 43 (2000) 2664-2674
13. Murray C.W., and Verdonk M.L. The consequences of translational and rotational entropy lost by small molecules on binding to proteins. J. Comp. Aided Mol. Design 16 (2002) 741-753
14. Hopkins A.L., et al. Ligand efficiency: a useful metric for lead selection. Drug Discov. Today 9 (2004) 430-431
15. Schuffenhauer A., et al. Library design for fragment based screening. Curr. Top. Med. Chem. 5 (2005) 751-762
16. Lepre C.A. Library design for NMR-based screening. Drug Discov. Today 6 (2001) 133-140
17. Wells J.A., and McClendon C.L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 450 (2007) 1001-1009
18. Petros A.M., et al. Discovery of a potent inhibitor of the antiapoptotic protein Bcl-xL from NMR and parallel synthesis. J. Med. Chem. 49 (2006) 656-663
19. Bruncko M., et al. Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL. J. Med. Chem. 50 (2007) 641-662
20. Edwards P.D., et al. Application of Fragment-based lead generation to the discovery of novel, cyclic amidine β-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency. J. Med. Chem. 50 (2007) 5912-5925
21. Carr R.A.E., et al. Fragment-based lead discovery: leads by design. Drug Discov. Today 10 (2005) 987-992
22. Siegal G., et al. Integration of fragment screening and library design. Drug Discov. Today 12 (2007) 1032-1039
23. Rees D.C., et al. Fragment-based lead discovery. Nat. Rev. Drug Discov. 3 (2004) 660-672
24. Rath V.L., et al. Human liver glycogen phosphorylase inhibitors bind at a new allosteric site. Chem. Biol. 7 (2000) 677-682
25. Hajduk P.J., et al. Design of adenosine kinase inhibitors from the NMR-based screening of fragments. J. Med. Chem. 43 (2000) 4781-4786
26. Lipinski C.A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 44 (2000) 235-249
27. Congreve M., et al. A 'Rule of Three' for fragment-based lead discovery?. Drug Discov. Today 8 (2003) 876-877
28. Baurin N., et al. Design and characterization of libraries of molecular fragments for use in NMR screening against protein targets. J. Chem. Info. Comp. Sci. 44 (2004) 2157-2166
29. Fattori D. Molecular recognition: the fragment approach in lead generation. Drug Discov. Today 9 (2004) 229-238
30. Fejzo J., et al. The SHAPES strategy: an NMR-based approach for lead generation in drug discovery. Chem. Biol. 6 (1999) 755-769
31. Kuntz I.D., et al. The maximal affinity of ligands. Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 9997-10002
32. Hajduk P.J. Fragment-Based drug design: how big is too big?. J. Med. Chem. 49 (2006) 6972-6976
33. Abad-Zapatero C., and Metz J.T. Ligand efficiency indices as guideposts for drug discovery. Drug Discov. Today 10 (2005) 464-469
34. Leeson P.D., and Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat. Rev. Drug Discov. 6 (2007) 881-890
35. Ciulli A., et al. Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods. J. Med. Chem. 49 (2006) 4992-5000
36. Saxty G., et al. Identification of inhibitors of protein kinase B using fragment-based lead discovery. J. Med. Chem. 50 (2007) 2293-2296
37. Reynolds C.H., et al. The role of molecular size in ligand efficiency. Bioorganic Med. Chem. Lett. 17 (2007) 4258-4261
38. Reynolds C.H., et al. Ligand binding efficiency: trends, physical basis, and implications. J. Med. Chem. 51 (2008) 2432-2438
39. Krier M., et al. Design of small-sized libraries by combinatorial assembly of linkers and functional groups to a given scaffold: application to the structure-based optimization of a phosphodiesterase 4 inhibitor. J. Med. Chem. 48 (2005) 3816-3822
40. Hochgurtel M., et al. Target-induced formation of neuraminidase inhibitors from in vitro virtual combinatorial libraries. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 3382-3387