Many drugs contain unique scaffolds with varying structural relationships to scaffolds of currently available bioactive compounds

European Journal of Medicinal Chemistry

Volumn 76, Issue , 2014, Pages 427-434

  Hu, Ye ^a   Bajorath, Jürgen ^a  

^a UNIVERSITY OF BONN   (Germany)

Author keywords

Approved drugs; Bioactive compounds; Drug unique scaffolds; Matched molecular pairs; Scaffolds; Substructure relationships; Topological equivalence

Indexed keywords

ARSENIC TRIOXIDE; CAPREOMYCIN; CARBOPLATIN; EFAVIRENZ; ERTAPENEM; ESZOPICLONE; FLUCONAZOLE; IFOSFAMIDE; IMIPENEM; KETAZOLAM; MOLECULAR SCAFFOLD; NEVIRAPINE; OXALIPLATIN; PHOTOFRIN; STIBOGLUCONATE SODIUM; THIOTEPA; TOLAZAMIDE; BIOMATERIAL; DRUG;

ARTICLE; BIOLOGICAL ACTIVITY; DRUG REPOSITIONING; DRUG UNIQUE; STRUCTURE ACTIVITY RELATION; CHEMICAL STRUCTURE; CHEMISTRY;

BIOCOMPATIBLE MATERIALS; MOLECULAR STRUCTURE; PHARMACEUTICAL PREPARATIONS;

EID: 84895557543     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.02.040     Document Type: Article

References (34)

1. N. Brown, and E. Jacoby On scaffolds and hopping in medicinal chemistry Mini-Reviews in Medicinal Chemistry 6 2006 1217 1229
2. Y. Hu, D. Stumpfe, and J. Bajorath Lessons learned from molecular scaffold analysis Journal of Chemical Information and Modeling 51 2011 1742 1753
3. G.W. Bemis, and M.A. Murcko The properties of known drugs. 1. Molecular frameworks Journal of Medicinal Chemistry 39 1996 2887 2893
4. H.B. Broughton, and I.A. Watson Selection of heterocycles for drug design Journal of Molecular Graphics and Modelling 23 2004 51 58
5. J. Wang, and T. Hou Drug and drug candidate building block analysis Journal of Chemical Information and Modeling 50 2010 55 67
6. Y.-J. Xu, and M. Johnson Using molecular equivalence numbers to visually explore structural features that distinguish chemical libraries Journal of Medicinal Chemistry 42 2002 912 926
7. R.P. Sheridan Finding multiactivity substructures by mining databases of drug-like compounds Journal of Molecular Graphics and Modelling 43 2003 1037 1050
8. G. Müller Medicinal chemistry of target family-directed masterkeys Drug Discovery Today 8 2003 681 691
9. D.M. Schnur, M.A. Hermsmeier, and A.J. Tebben Are target-family- privileged substructures truly privileged? Journal of Medicinal Chemistry 49 2006 2000 2009
10. J.J. Sutherland, R.E. Higgs, I. Watson, and M. Vieth Chemical fragments as foundations for understanding target space and activity prediction Journal of Medicinal Chemistry 51 2008 2689 2700
11. S. Renner, W.A.L. Van Otterlo, M.D. Seoane, S. Möcklinghoff, B. Hoffmann, S. Wetzel, A. Schuffenhauer, P. Ertl, T.I. Oprea, D. Steinhilber, L. Brunsveld, D. Rauh, and H. Waldmann Bioactivity-guided mapping and navigation of chemical space Nature Chemical Biology 5 2009 585 592
12. X.Q. Lewell, D.B. Judd, S.P. Watson, and M.M. Hann RECAP - retrosynthetic combinatorial analysis procedure: a powerful new technique for identifying privileged molecular fragments with useful applications in combinatorial chemistry Journal of Molecular Graphics and Modelling 38 1998 511 522
13. S.J. Wilkens, J. Janes, and A.I. Su HierS: hierarchical scaffold clustering using topological chemical graphs Journal of Medicinal Chemistry 48 2005 182 193
14. A. Schuffenhauer, P. Ertl, S. Roggo, S. Wetzel, M.A. Koch, and H. Waldmann The scaffold tree - visualization of the scaffold universe by hierarchical scaffold classification Journal of Chemical Information and Modeling 47 2007 47 58
15. D. Gupta-Ostermann, Y. Hu, and J. Bajorath Introducing the LASSO graph for compound data set representation and structure-activity relationship analysis Journal of Medicinal Chemistry 55 2012 5546 5553
16. S. Wetzel, K. Klein, S. Renner, D. Rauh, T.I. Oprea, P. Mutzel, and H. Waldmann Interactive exploration of chemical space with scaffold hunter Nature Chemical Biology 5 2009 581 583
17. S. Wetzel, W. Wilk, S. Chammaa, B. Sperl, A.G. Roth, A. Yektaoglu, S. Renner, T. Berg, A. Arenz, A. Giannis, T.I. Oprea, D. Rauh, M. Kaiser, and H. Waldmann A scaffold-tree-merging strategy for prospective bioactivity annotation of γ-pyrones Angewandte Chemie International Edition 122 2010 3748 3752
18. Y. Hu, and J. Bajorath Scaffold distributions in bioactive molecules, clinical trials compounds, and drugs ChemMedChem 5 2010 187 190
19. Y. Hu, and J. Bajorath Polypharmacology directed data mining: identification of promiscuous chemotypes with different activity profiles and comparison to approved drugs Journal of Chemical Information and Modeling 50 2010 2112 2118
20. G.V. Paolini, R.H.B. Shapland, W.P. van Hoorn, J.S. Mason, and A.L. Hopkins Global mapping of pharmacological space Nature Biotechnology 24 2006 805 815
21. A.D.W. Boran, and R. Iyengar Systems approaches to polypharmacology and drug discovery Current Opinion in Drug Discovery & Development 13 2010 297 309
22. R. Bade, H.-F. Chan, and J. Reynisson Characteristics of known drug space. Natural products, their derivatives, and synthetic drugs European Journal of Medicinal Chemistry 45 2010 5646 5652
23. A. Gaulton, L.J. Bellis, A.P. Bento, J. Chambers, M. Davies, A. Hersey, Y. Light, S. McGlinchey, D. Michalovich, B. Al-Lazikani, and J.P. Overington ChEMBL: a large-scale bioactivity database for drug discovery Nucleic Acids Research 40 2012 D1100 D1107
24. C. Knox, V. Law, T. Jewison, P. Liu, S. Ly, A. Frolkis, A. Pon, K. Banco, C. Mak, V. Neveu, Y. Djoumbou, R. Eisner, A.C. Guo, and D.S. Wishart DrugBank 3.0: a comprehensive resource for 'omics' research on drugs Nucleic Acids Research 39 2011 D1035 D1041
25. P.W. Kenny, and J. Sadowski Structure modification in chemical databases T.I. Oprea, Chemoinformatics in Drug Discovery 2004 Wiley-VCH Weinheim, Germany 271 285
26. J. Hussain, and C. Rea Computationally efficient algorithm to identify matched molecular pairs (MMPs) in large data sets Journal of Chemical Information and Modeling 50 2010 339 348
27. X. Hu, Y. Hu, M. Vogt, D. Stumpfe, and J. Bajorath MMP-cliffs: systematic identification of activity cliffs on the basis of matched molecular pairs Journal of Chemical Information and Modeling 52 2012 1138 1145
28. OEChem TK, Version 20111017, release 1.7.6; OpenEye Scientific Software Inc.: Santa Fe, New Mexico.
29. Molecular Operating Environment (MOE), 2011.10 2011 Chemical Computing Group Inc. 1010 Sherbooke St. West, Suite#910, Montreal, QC, Canada, H3A 2R7
30. P.D. Leeson, and B. Springthorpe The influence of drug-like concepts on decision-making in medicinal chemistry Nature Reviews Drug Discovery 6 2007 881 890
31. C.A. Lipinski, F. Lombardo, B.W. Dominy, and P.J. Feeney Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Advanced Drug Delivery Reviews 23 1997 3 25
32. P. Axerion-Cilies, I.P. Castaneda, A. Mirza, and J. Reynisson Investigation of the incidence of "undesirable" molecular moieties for high-throughput screening compound libraries in marketed drug compounds European Journal of Medicinal Chemistry 44 2009 1128 1134
33. C.R. Chong, and D.J. Sullivan New uses for old drugs Nature 448 2006 645 646
34. Y. Hu, J. Bajorath, Drug-unique scaffolds, ZENODO.10.5281/zenodo.8358.