Lead optimization using matched molecular pairs: Inclusion of contextual information for enhanced prediction of hERG inhibition, solubility, and lipophilicity

Journal of Chemical Information and Modeling

Volumn 50, Issue 10, 2010, Pages 1872-1886

  Papadatos, George ^a   Alkarouri, Muhammad ^a   Gillet, Valerie J ^a   Willett, Peter ^a   Kadirkamanathan, Visakan ^a   Luscombe, Christopher N ^b   Bravi, Gianpaolo ^b   Richmond, Nicola J ^b   Pickett, Stephen D ^b   Hussain, Jameed ^b   Pritchard, John M ^b   Cooper, Anthony W J ^b   MacDonald, Simon J F ^b  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMICAL ENGINEERING; CHEMISTRY;

CONTEXT INDEPENDENT; CONTEXTUAL INFORMATION; LEAD OPTIMIZATION; LIPOPHILICITY; MOLECULAR PAIRS; MOLECULAR PROPERTIES; PREDICTIVE POWER; STRUCTURAL ENVIRONMENT;

SOLUBILITY;

LIGAND; LIPID; POTASSIUM CHANNEL HERG;

ALGORITHM; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; DRUG DESIGN; FACTUAL DATABASE; HUMAN; METABOLISM; SOLUBILITY;

ALGORITHMS; DATABASES, FACTUAL; DRUG DESIGN; ETHER-A-GO-GO POTASSIUM CHANNELS; HUMANS; LIGANDS; LIPIDS; MOLECULAR STRUCTURE; SOLUBILITY;

EID: 77958518144     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci100258p     Document Type: Article

References (30)

1. Leach, A. R.; Gillet, V. J. An Introduction to Chemoinformatics. 2nd ed.; Kluwer: Dordrecht, The Netherlands, 2007.
2. Sheridan, R. P. The most common chemical replacements in drug-like compounds J. Chem. Inf. Comput. Sci. 2002, 42, 103-108
3. Holliday, J. D.; Jelfs, S. P.; Willett, P. Calculation of intersubstituent similarity using R-group descriptors J. Chem. Inf. Comput. Sci. 2003, 43, 406-411
4. Wagener, M.; Lommerse, J. P. M. The quest for bioisosteric replacements J. Chem. Inf. Model. 2006, 46, 677-685
5. Krier, M.; Hutter, M. C. Bioisosteric similarity of molecules based on structural alignment and observed chemical replacements in drugs J. Chem. Inf. Model. 2009, 49, 1280-1297
6. Birchall, K.; Gillet, V. J.; Willett, P.; Ducrot, P.; Luttmann, C. Use of reduced graphs to encode bioisosterism for similarity-based virtual screening J. Chem. Inf. Model. 2009, 49, 1330-1346
7. Hansch, C.; Maloney, P. P.; Fujita, T.; Muir, R. M. Correlation of biological activity of phenoxyacetic acids with Hammett substituent constants and partition coefficients Nature 1962, 194, 178-180
8. Free, S. M.; Wilson, J. W. A mathematical contribution to structure-activity studies J. Med. Chem. 1964, 7, 395-399
9. Cramer, R. D.; Patterson, D. E.; Bunce, J. D. Comparative Molecular-Field Analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins J. Am. Chem. Soc. 1988, 110, 5959-5967
10. Hansch, C.; Hoekman, D.; Leo, A.; Weininger, D.; Selassie, C. D. Chem-Bioinformatics: Comparative QSAR at the Interface between Chemistry and Biology Chem. Rev. 2002, 102, 783-812
11. Lewis, R. A. A general method for exploiting QSAR models in lead optimization J. Med. Chem. 2005, 48, 1638-1648
12. Haubertin, D. Y.; Bruneau, P. A database of historically-observed chemical replacements J. Chem. Inf. Model. 2007, 47, 1294-1302
13. Sheridan, R. P.; Hunt, P.; Culbertson, J. C. Molecular transformations as a way of finding and exploiting consistent local QSAR J. Chem. Inf. Model. 2006, 46, 180-192
14. Hajduk, P. J.; Sauer, D. R. Statistical analysis of the effects of common chemical substituents on ligand potency J. Med. Chem. 2008, 51, 553-564
15. Lewis, M. L.; Cucurull-Sanchez, L. Structural pairwise comparisons of HLM stability of phenyl derivatives: Introduction of the Pfizer metabolism index (PMI) and metabolism-lipophilicity efficiency (MLE) J. Comput.-Aided Mol. Des. 2009, 23, 97-103
16. Gleeson, P.; Bravi, G.; Modi, S.; Lowe, D. ADMET rules of thumb II: A comparison of the effects of common substituents on a range of ADMET parameters Bioorg. Med. Chem. 2009, 17, 5906-5919
17. Birch, A. M.; Kenny, P. W.; Simpson, I.; Whittamore, P. R. O. Matched molecular pair analysis of activity and properties of glycogen phosphorylase inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 850-853
18. Southall, N. T.; Ajay Kinase patent space visualization using chemical replacements J. Med. Chem. 2006, 49, 2103-2109
19. Raymond, J. W.; Watson, I. A.; Mahoui, A. Rationalizing lead optimization by associating quantitative relevance with molecular structure modification J. Chem. Inf. Model. 2009, 49, 1952-1962
20. 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
21. Leach, A. G.; Jones, H. D.; Cosgrove, D. A.; Kenny, P. W.; Ruston, L.; MacFaul, P.; Wood, J. M.; Colclough, N.; Law, B. Matched molecular pairs as a guide in the optimization of pharmaceutical properties: A study of aqueous solubility, plasma protein binding and oral exposure J. Med. Chem. 2006, 49, 6672-6682
22. Jamieson, C.; Moir, E. M.; Rankovic, Z.; Wishart, G. Medicinal chemistry of hERG optimizations: Highlights and hang-ups J. Med. Chem. 2006, 49, 5029-5046
23. Kerns, E. H.; Di, L. Drug-Like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization; Academic Press: San Diego, CA, 2008.
24. Bhattachar, S. N.; Wesley, J. A.; Seadeek, C. Evaluation of the chemiluminescent nitrogen detector for solubility determinations to support drug discovery J. Pharm. Biomed. Anal. 2006, 41, 152-157
25. Harper, G.; Bravi, G. S.; Pickett, S. D.; Hussain, J.; Green, D. V. S. The reduced graph descriptor in virtual screening and data-driven clustering of high-throughput screening data J. Chem. Inf. Comput. Sci. 2004, 44, 2145-2156
26. Bemis, G. W.; Murcko, M. A. The properties of known drugs. 1. Molecular frameworks J. Med. Chem. 1996, 39, 2887-2893
27. Accelrys Pipeline Pilot, version 7.0; Accelrys Inc.: San Diego, CA, 2010.
28. Bender, A.; Mussa, H. Y.; Glen, R. C.; Reiling, S. Molecular similarity searching using atom environments: Information-based feature selection and a naive Bayesian classifier J. Chem. Inf. Comput. Sci. 2004, 44, 170-178
29. Lobell, M.; Hendrix, M.; Hinzen, B.; Keldenich, J.; Meier, H.; Schmeck, C.; Schohe-Loop, R.; Wunberg, T.; Hillisch, A. In silico ADMET traffic lights as a tool for the prioritization of HTS hits ChemMedChem 2006, 1, 1229-1236
30. Waring, M. J. Lipophilicity in drug discovery Expert Opin. Drug Discovery 2010, 5, 235-248