Matched molecular pair analysis of small molecule microarray data identifies promiscuity cliffs and reveals molecular origins of extreme compound promiscuity

Journal of Medicinal Chemistry

Volumn 55, Issue 22, 2012, Pages 10220-10228

  Dimova, Dilyana ^a   Hu, Ye ^a   Bajorath, Jürgen ^a  

^a UNIVERSITY OF BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

MOLECULAR SCAFFOLD;

ARTICLE; CHEMICAL MODIFICATION; MICROARRAY ANALYSIS;

CHEMISTRY, PHARMACEUTICAL; DRUG DISCOVERY; HUMANS; MICROARRAY ANALYSIS; MOLECULAR STRUCTURE; PHARMACEUTICAL PREPARATIONS; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84870012905     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301292a     Document Type: Article

References (28)

1. Feng, B. Y.; Shelat, A.; Doman, T. N.; Guy, R. K.; Shoichet, B. K. High-Throughput Assays for Promiscuous Inhibitors Nat. Chem. Biol. 2005, 1, 146-148
2. Paolini, G. V.; Shapland, R. H. B.; van Hoorn, W. P.; Mason, J. S.; Hopkins, A. L. Global Mapping of Pharmacological Space Nat. Biotechnol. 2006, 24, 805-815
3. Keiser, M. J.; Roth, B. L.; Armbruster, B. N.; Ernsberger, P.; Irwin, J. J.; Shoichet, B. K. Relating Protein Pharmacology by Ligand Chemistry Nat. Biotechnol. 2007, 25, 197-206
4. Hopkins, A. L. Network Pharmacology: The Next Paradigm in Drug Discovery Nat. Chem. Biol. 2008, 4, 682-690
5. Keiser, M. J.; Setola, V.; Laggner, C.; Abbas, A. I.; Hufeisen, S. J.; Jensen, N. H.; Kuijer, M. B.; Matos, R. C.; Tran, T. B.; Whaley, R.; Glennon, R. A.; Hert, J.; Thomas, K. L.; Edwards, D. D.; Shoichet, B. K.; Roth, B. L. Predicting New Molecular Targets for Known Drugs Nature 2009, 462, 175-181
6. Ashburn, T. T.; Thor, K. B. Drug Repositioning: Identifying and Developing New Uses for Existing Drugs Nat. Rev. Drug Discovery 2004, 3, 673-683
7. Chong, C. R.; Sullivan, D. J. New Uses for Old Drugs Nature 2007, 448, 645-646
8. Mestres, J.; Gregori-Puigjané, E. Conciliating Binding Efficiency and Polypharmacology Trends Pharmacol. Sci. 2009, 30, 470-474
9. Merino, A.; Bronowska, A. K.; Jackson, D. B.; Cahill, D. J. Drug Profiling: Knowing Where It Hits Drug Discovery Today 2010, 15, 749-756
10. Koutsoukas, A.; Simms, B.; Kirchmair, J.; Bond, P. J.; Whitmore, A. V.; Zimmer, S.; Young, M. P.; Jenkins, J. L.; Glick, M.; Glen, R. C.; Bender, A. From in Silico Target Prediction to Multi-Target Drug Design: Current Databases, Methods and Applications J. Proteomics 2011, 74, 2554-2574
11. Xie, L.; Xie, L.; Kinnings, S. L.; Bourne, P. E. Novel Computational Approaches to Polypharmacology as a Means to Define Responses to Individual Drugs Annu. Rev. Pharmacol. Toxicol. 2012, 52, 361-379
12. Hu, Y.; Bajorath, J. Polypharmacology Directed Compound Data Mining: Identification of Promiscuous Chemotypes with Different Activity Profiles and Comparison to Approved Drugs J. Chem. Inf. Model. 2010, 50, 2112-2118
13. Campillos, M.; Kuhn, M.; Gavin, A. C.; Jensen, L. J.; Bork, P. Drug Target Identification Using Side-Effect Similarity Science 2008, 321, 263-266
14. Gaulton, A.; Bellis, L. J.; Bento, A. P.; Chambers, J.; Davies, M.; Hersey, A.; Light, Y.; McGlinchey, S.; Michalovich, D.; Al-Lazikani, B.; Overington, J. P. ChEMBL: A Large-Scale Bioactivity Database for Drug Discovery Nucleic Acids Res. 2012, 40, D1100-D1107
15. Wang, Y.; Xiao, J.; Suzek, T. O.; Zhang, J.; Wang, J.; Zhou, Z.; Han, L.; Karapetyan, K.; Dracheva, S.; Shoemaker, B. A.; Bolton, E.; Gindulyte, A.; Bryant, S. H. PubChem's Bioassay Database Nucleic Acids Res. 2012, 40, D400-D412
16. Metz, J. T.; Johnson, E. F.; Soni, N. B.; Merta, P. J.; Kifle, L.; Hajduk, P. J. Navigating the Kinome Nat. Chem. Biol. 2011, 7, 200-202
17. Iyer, P.; Dimova, D.; Vogt, M.; Bajorath, J. Navigating High-Dimensional Activity Landscapes: Design and Application of the Ligand-Target Differentiation Map J. Chem. Inf. Model. 2012, 52, 1962-1969
18. Clemons, P. A.; Bodycombe, N. E.; Carrinski, H. A.; Wilson, J. A.; Shamji, A. F.; Wagner, B. K.; Koehler, A. N.; Schreiber, S. L. Small Molecules of Different Origins Have Distinct Distributions of Structural Complexity that Correlate with Protein-Binding Profiles Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 18787-18792
19. Interpro Sequence Analysis & Classification, www.ebi.ac.uk/interpro/ (Accessed August 14, 2012).
20. Kenny, P. W.; Sadowski, J. Structure Modification in Chemical Databases. In Chemoinformatics in Drug Discovery; Oprea, T. I., Ed.; Wiley-VCH: Weinheim, Germany, 2004; pp 271-285.
21. Molecular Operating Environment (MOE), 2011.10; Chemical Computing Group Inc., 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2011.
22. Weininger, D. SMILES, a Chemical Language and Information System. 1. Introduction to Methodology and Encoding Rules J. Chem. Inf. Comput. Sci. 1988, 28, 31-36
23. Hussain, J.; Rea, C. Computationally Efficient Algorithm To Identify Matched Molecular Pairs (MMPs) in Large Data Sets J. Chem. Inf. Model. 2010, 50, 339-348
24. Wassermann, A. M.; Bajorath, J. Chemical Substitutions That Introduce Activity Cliffs across Different Compound Classes and Biological Targets J. Chem. Inf. Model. 2010, 50, 1248-1256
25. Wassermann, A. M.; Bajorath, J. Large-Scale Exploration of Bioisosteric Replacements on the Basis of Matched Molecular Pairs Future Med. Chem. 2011, 3, 425-436
26. Hu, X.; Hu, Y.; Vogt, M.; Stumpfe, D.; Bajorath, J. MMP-Cliffs: Systematic Identification of Activity Cliffs on the Basis of Matched Molecular Pairs J. Chem. Inf. Model. 2012, 52, 1138-1145
27. Tiwaria, A.; Sekhar, A. K. T. Workflow Based Framework for Life Science Informatics Comput. Biol. Chem. 2007, 31, 305-319
28. Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N. S.; Wang, J. T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks Genome Res. 2003, 13, 2498-2504