The Scaffold Tree: An Efficient Navigation in the Scaffold Universe

Methods in Molecular Biology

Volumn 672, Issue , 2011, Pages 245-260

  Ertl, Peter ^a   Schuffenhauer, Ansgar ^a   Renner, Steffen ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Chemical space; Clustering; Ring; Scaffold; Scaffold classification; Scaffold hopping; Scientific visualization

Indexed keywords

COSMOS; INTERNET; MEDICINAL CHEMISTRY; PLANT LEAF; SOFTWARE; ALGORITHM; CHEMICAL STRUCTURE; CHEMISTRY; CLUSTER ANALYSIS; COMPUTER PROGRAM; COMPUTER SIMULATION; FACTUAL DATABASE; METHODOLOGY; REVIEW;

DRUG;

ALGORITHMS; CHEMISTRY, PHARMACEUTICAL; CLUSTER ANALYSIS; COMPUTER SIMULATION; DATABASES, FACTUAL; INTERNET; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PHARMACEUTICAL PREPARATIONS; SOFTWARE;

EID: 79952118881     PISSN: 10643745     EISSN: 19406029     Source Type: Book Series    
DOI: 10.1007/978-1-60761-839-3_10     Document Type: Chapter

References (33)

1. Brown, N. and Jacoby, E. (2006) On Scaffolds and Hopping in Medicinal Chemistry. Mini Rev. Med. Chem. 6, 1217–1229.
2. Schneider, G., Schneider, P., and Renner, S. (2006) Scaffold-Hopping: How far can you Jump? QSAR Comb. Sci. 25, 1162–1171.
3. Bemis, G. W. and Murcko, M. A. (1996) The Properties of Known Drugs. 1. Molecular Frameworks. J. Med. Chem. 39, 2887–2893.
4. Lipkus, A. (2001) Exploring Chemical Rings in a Simple Topological-Descriptor Space. J. Chem. Inf. Comput. Sci. 41, 430–438.
5. Lipkus, A. H., Yuan, Q., Lucas, K. A., Funk, S. A., Bartelt, III, W. F., Schenck, R. J., and Trippe, A. J. (2008) Structural Diversity of Organic Chemistry. A Scaffold Analysis of the CAS Registry. J. Org. Chem. 73, 4443– 4451.
6. Wilkens, S., Janes, J., and Su, A. (2005) HierS: Hierarchical Scaffold Clustering Using Topological Chemical Graphs. J. Med. Chem. 48, 3182–3193.
7. Ertl, P., Jelfs, S., Muehlbacher, J., Schuffenhauer, A., and Selzer, P. (2006) Quest for the Rings. In Silico Exploration of Ring Universe to Identify Novel Bioactive Heteroaromatic Scaffolds. J. Med. Chem. 49, 4568–4573.
8. Pitt, W. R., Parry, D. M., Perry, B. G., and Groom, C. R. (2009) Heteroaromatic Rings of the Future. J. Med. Chem. 52, 2952–2963.
9. Wester, M. J., Pollock, S. N., Coutsias, E. A., Allu, T. K., Muresan, S., and Oprea, T. I. (2008) Scaffold Topologies. 2. Analysis of Chemical Databases. J. Chem. Inf. Model. 48, 1311–1324.
10. Schuffenhauer, A., Ertl, P., Roggo, S., Wetzel, S., Koch, M. A., and Waldmann, H. (2007) The Scaffold Tree–Visualization of the Scaffold Universe by Hierarchical Scaffold Classification. J. Chem. Inf. Model. 47, 47–58.
11. Weininger, D. (1988) SMILES, a Chemical Language and Information System. 1. Introduction to Methodology and Encoding Rules. J. Chem. Inf. Comput. Sci. 28, 31–36.
12. http://www.iupac.org/inchi/.
13. Koch, M., Schuffenhauer, A., Scheck, M., Wetzel, S., Casaulta, M., Odermatt, A., Ertl, P., and Waldmann, H. (2005) Charting Biologically Relevant Chemical Space: A Structural Classification of Natural Products (SCONP). Proc. Natl. Acad. Sci. U.S.A. 102, 17272–17277.
14. Renner, S., van Otterlo, W. A. L., Dominguez Seoane, M., Moecklinghoff, S., Hofmann, B., Wetzel, S., Schuffenhauer, A., Ertl, P., Oprea, T. I., Steinhilber, D., Brunsveld, L., Rauh, D., and Waldmann H. (2009) Bioactivity-Guided Mapping and Navigation of Chemical Space. Nature Chem. Biol. 5, 585–592.
15. http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=628.
16. GVK MedChem Database, GVK Biosciences, http://www.gvkbio.com/.
17. Schuffenhauer, A., Brown, N., Ertl, P., Jenkins, J. L., Selzer, P., and Hamon, J. (2007) Clustering and Rule-Based Classifications of Chemical Structures Evaluated in the Biological Activity Space. J. Chem. Inf. Model. 47, 325–336.
18. Kelley, L. A., Gardner, S. P., and Sutcliffe, M. J. (1996) An Automated Approach for Clustering an Ensemble of NMR-Derived Protein Structures into Conformationally Related Sub-families. Protein Eng. 9, 1063–1065.
19. Clark, R. D. (1997) OptiSim: An Extended Dissimilarity Selection Method for Finding Diverse Representative Subsets. J. Chem. Inf. Comput. Sci. 37, 1181–1188.
20. Engels, M. F. M., Gibbs, A. C., Jaeger, E. P., Verbinnen, D., Lobanov, V. S., and Agrafiotis, D. K. (2006) A Cluster-Based Strategy for Assessing the Overlap between Large Chemical Libraries and Its Application to a Recent Acquisition. J. Chem. Inf. Model. 46, 2651– 2660.
21. MacCuish, J., Nicolaou, C., and MacCuish, N. E. (2001) Ties in Proximity and Clustering Compounds. J. Chem. Inf. Comput. Sci. 41, 134–146.
22. Hubert, L. and Arabie, P. (1985) Comparing Partitions. J. Classif. 2, 193–218.
23. Xu, Y. J. and Johnson, M. (2002) Using Molecular Equivalence Numbers To Visually Explore Structural Features that Distinguish Chemical Libraries. J. Chem. Inf. Comput. Sci. 42, 912–926.
24. Huebel, K., Lessmann, T., and Waldmann, H. (2008) Chemical Biology-Identification of Small Molecule Modulators of Cellular Activity by Natural Product Inspired Synthesis. Chem. Soc. Rev. 37, 1361–1374.
25. Lessmann, T., Leuenberger, M., Menninger, S., Lopez-Canet, M., Müller, O., Hümmer, S., Bormann, J., Korn, K., Fava, E., Zerial M., Mayer, T. U., and Waldmann, H. (2007) Natural Product-Derived Modulators of Cell Cycle Progression and Viral Entry by Enan-tioselective Oxa Diels-Alder Reactions on the Solid Phase. Chem. Biol. 14, 443–451.
26. Barun, O., Kumar, K., Sommer, S., Langerak, A., Mayer, T. U., and Waldmann, H. (2005) Natural Product-Guided Synthesis of a Spiroa-cetal Collection Reveals Modulators of Tubulin Cytoskeleton Integrity. Eur. J. Org. Chem. 22, 4773–4788.
27. Nören-Müller, A., Reis-Correa, I., Prinz, H., Rosenbaum, C., Saxena, K., Schwalbe, H. J., Vestweber, D., Cagna, G., Schunk, S., Schwarz, O., Schiewe, H., and Waldmann, H. (2006) Discovery of Protein Phosphatase Inhibitor Classes by Biology-Oriented Synthesis. Proc. Natl. Acad. Sci. U.S.A. 103, 10606–10611.
28. Wetzel, S., Klein, K., Renner, S., Rauh, D., Oprea, T. I., Mutzel, P., and Waldmann, H. (2009) Interactive exploration of chemical space with Scaffold Hunter. Nature Chem. Biol. 5, 581–583. http://sourceforge.net/projects/scaffoldhunter/.
29. Clark, A. M., and Labute, P. (2008) Detection and Assignment of Common Scaffolds in Project Databases of Lead Molecules. J. Med. Chem. 52, 469–483.
30. http://molwind.sourceforge.net/.
31. http://www.molinspiration.com/docu/clusterer/.
32. http://www.xemistry.com/edit/frame.html.
33. Ertl, P. and Jelfs, S. (2007) Designing Drugs on the Internet? Free Web Tools and Services Supporting Medicinal Chemistry. Curr. Top. Med. Chem. 7, 1491–1501.