Size estimation of chemical space: How big is it?

Journal of Pharmacy and Pharmacology

Volumn 64, Issue 4, 2012, Pages 490-495

  Drew, Kurt L M ^a   Baiman, Hakim ^a   Khwaounjoo, Prashanna ^a   Yu, Bo ^a   Reynisson, Jóhannes ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

drug characterisation studies; other topics

Indexed keywords

DRUG; ORGANIC COMPOUND;

ARTICLE; CHEMICAL PARAMETERS; DRUG BIOAVAILABILITY; DRUG LIKE CHEMICAL SPACE; KNOWN DRUG SPACE; ORGANIC CHEMICAL SPACE; PREDICTION; STATISTICAL DISTRIBUTION;

BIOLOGICAL AVAILABILITY; DATA INTERPRETATION, STATISTICAL; HUMANS; MODELS, CHEMICAL; MOLECULAR STRUCTURE; ORGANIC CHEMICALS; PHARMACEUTICAL PREPARATIONS;

EID: 84859105504     PISSN: 00223573     EISSN: 20427158     Source Type: Journal    
DOI: 10.1111/j.2042-7158.2011.01424.x     Document Type: Article

References (38)

1. Muchmore SW, et al,. Cheminformatic tools for medicinal chemists. J Med Chem 2010; 53: 4830-4841.
2. Reymond J-L, et al,. Chemical space as a source for new drugs. Med Chem Comm 2010; 1: 30-38.
3. Leeson PD, Springthorpe B,. The influence of drug-like concepts on decision making in medicinal chemistry. Nat Rev Drug Dis 2007; 6: 881-890. (Pubitemid 350042396)
4. Medina-Franco JL, et al,. Visualization of the chemical space in drug discovery. Curr Comp Aided Drug Des 2008; 4: 322-333.
5. Lipinski CA, et al,. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development setting. Adv Drug Deliv Rev 1997; 23: 3-25. (Pubitemid 27046991)
6. Lipinski CA,. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 2004; 1: 337-341. (Pubitemid 40186335)
7. Palm K, et al,. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm Res 1997; 14: 568-571. (Pubitemid 27220272)
8. Veber DF, et al,. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 2002; 45: 2615-2623. (Pubitemid 34595232)
9. Lu JJ, et al,. Influence of molecular flexibility and polar surface area metrics on oral bioavailability in the rat. J Med Chem 2004; 47: 6104-6107. (Pubitemid 39507351)
10. Rishton GM,. Reactive compounds and in vitro false positives in HTS. Drug Discov Today 1997; 9: 382-384. (Pubitemid 27368216)
11. Rishton GM,. Nonleadlikeness and leadlikeness in biochemical screening. Drug Discov Today 2003; 8: 86-96. (Pubitemid 36139902)
12. Baell JB, Holloway GA,. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem 2010; 53: 2719-2740.
13. Mcgovern SL, et al,. A specific mechanism of nonspecific inhibitors. J Med Chem 2003; 46: 4265-4272.
14. Jadhav A, et al,. Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease. J Med Chem 2010; 53: 37-51.
15. Lipinski CA,. Properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods 2000; 44: 235-249. (Pubitemid 32239479)
16. Oprea TI,. Current trends in lead discovery: are we looking for the appropriate properties? Mol Divers 2000; 5: 199-208. (Pubitemid 36082830)
17. Oprea TI, et al,. Is there a difference between leads and drugs? A historical perspecitve. J Chem Inf Comput Sci 2001; 41: 1308-1315.
18. Chen Y, Shoichet BK,. Molecular docking and ligand specificity in fragment-based inhibitor discovery. Nature Chem Biol 2009; 5: 358-364.
19. Axerio-Cilies P, et al,. Investigation of the incidence of 'undesirable' molecular moieties for high-throughput screening compound libraries in marketed drug compounds. Eur J Med Chem 2009; 44: 1128-1134.
20. Bade R, et al,. Characteristics of known drug space. Natural products, their derivatives and synthetic drugs. Eur J Med Chem 2010; 45: 5646-5652.
21. Mirza A, et al,. Known drug space as a metric in determining the boundaries of drug-like chemical space. Eur J Med Chem 2009; 44: 5006-5011.
22. Bohacek RS, et al,. The art and practice of structure-based drug design: a molecular modeling perspective. Med Res Rev 1996; 16: 3-50. (Pubitemid 26037075)
23. Fink T, et al,. Virtual exploration of the small-molecule chemical universe below 160 daltons. Angew Chem Int Ed Engl 2005; 44: 1504-1508. (Pubitemid 40460043)
24. Windholz M, et al,. The Merck Index, 9th edn. Rahway: Merck & Co. Inc., 1976.
25. Lide DR,. Formula index for organic compounds. In:, Lide DR, ed. Handbook of Chemistry and Physics. London: CRC Press, 1993: 3-601-633.
26. ChemSpider database.
27. NIST Webbook.
28. Wishart DS, et al,. DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucl Acids Res 2008; 36: D901-D906. (Pubitemid 351149842)
29. Wishart DS, et al,. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucl Acids Res 2006; 34: D668-D672.
30. Chemnetbase database. Dictionary of Drugs. Taylor & Francis Group, 2011.
31. Clauset A, et al,. Power-law distributions in empirical data. SIAM Rev 2009; 4: 661-703.
32. Ertl P,. Cheminformatics analysis of organic substituents: identification of the most common substituent, calculations of substituents properties, and automatic identification of drug-like bioisoteric groups. J Chem Inf Comput Sci 2003; 43: 374-380.
33. Geysen HM, et al,. A guide to drug discovery: combinatorial compound libraries for drug discovery: an ongoing challenge. Nat Rev Drug Dis 2003; 2: 222-230. (Pubitemid 37361667)
34. Ogata K, et al,. A quantitative approach to the estimation of chemical space from a given geometry by the combination of atomic species. QSAR Comb Sci 2007; 26: 596-607. (Pubitemid 46938089)
35. Fink T, Reymond J-L,. Virtual exploration of the chemical universe up to 11 atoms of C, N, O, F: assembly of 26.4 million structures (110.9 million stereoisomers) and analysis for new ring systems, stereochemistry, physicochemical properties, compound classes, and drug discovery. J Chem Inf Model 2007; 47: 342-353. (Pubitemid 46615939)
36. Blum LC, Reymond J-L,. 970 million drug-like small molecules for virtual screening in the chemical universe database GDB-13. J Am Chem Soc 2009; 131: 8732-8733.
37. Weaver DF, Weaver CA,. Exploring neurotherapeutic space: how many neurological drugs exist (or could exist)? J Pharm Pharmacol 2011; 63: 136-139.
38. Nicolaou KC, Montagnon T,. Molecules That Changed the World. Weinheim: Wiley-VCH Verlag GmbH, 2008.