Investigation of the relationship between topology and selectivity for druglike molecules

Journal of Medicinal Chemistry

Volumn 53, Issue 21, 2010, Pages 7709-7714

  Yang, Yidong ^a   Chen, Hongming ^a   Nilsson, Ingemar ^a   Muresan, Sorel ^a   Engkvist, Ola ^a  

^a ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

EZETIMIBE; LAMOTRIGINE;

ARTICLE; CONCEPTUAL FRAMEWORK; DRUG DEVELOPMENT; DRUG SELECTIVITY; DRUG STRUCTURE; HUMAN; LIPOPHILICITY; MOLECULAR SIZE;

DATABASES, FACTUAL; DRUG DISCOVERY; MOLECULAR STRUCTURE; PHARMACEUTICAL PREPARATIONS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78149236457     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm1008456     Document Type: Article

References (25)

1. Druker, B. J. STI571 (Gleevec) as a paradigm for cancer therapy Trends Mol. Med. 2002, 8, S14-S18
2. Kalgutkar, A. S.; Crews, B. C.; Rowlinson, S. W.; Marnett, A. B.; Kozak, K. R.; Remmel, R. P.; Marnett, L. J. Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 925-930
3. Mencher, S.; Wang, L. Promiscuous drugs compared to selective drugs (promiscuity can be a virtue) BMC Clin. Pharmacol. 2005, 5, 3
4. Stephenson, V. C.; Heyding, R. A.; Weaver, D. F. The "promiscuous drug concept" with applications to Alzheimer's disease FEBS Lett. 2005, 579, 1338-1342
5. Roth, B. L.; Sheffler, D. J.; Kroeze, W. K. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia Nat. Rev. Drug Discovery 2004, 3, 353-359
6. Hampton, T. "Promiscuous" anticancer drugs that hit multiple targets may thwart resistance JAMA, J. Am. Med. Assoc. 2004, 292, 419-422
7. Azzaoui, K.; Hamon, J.; Faller, B.; Whitebread, S.; Jacoby, E.; Bender, A.; Jenkins, J. L.; Urban, L. Modeling promiscuity based on in vitro safety pharmacology profiling data ChemMedChem 2007, 2, 874-880
8. Rolland, C.; Gozalbes, R.; Nicolai, E.; Paugam, M.-F.; Coussy, L.; Barbosa, F.; Horvath, D.; Revah, F. G-Protein-coupled receptor affinity prediction based on the use of a profiling dataset: QSAR design, synthesis, and experimental validation J. Med. Chem. 2005, 48, 6563-6574
9. Fliri, A. F.; Loging, W. T.; Thadeio, P. F.; Volkmann, R. A. Biological spectra analysis: linking biological activity profiles to molecular structure Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 261-266
10. Roche, O.; Schneider, P.; Zuegge, J.; Guba, W.; Kansy, M.; Alanine, A.; Bleicher, K.; Danel, F.; Gutknecht, E.-M.; Rogers-Evans, M.; Neidhart, W.; Stalder, H.; Dillon, M.; Sjogren, E.; Fotouhi, N.; Gillespie, P.; Goodnow, R.; Harris, W.; Jones, P.; Taniguchi, M.; Tsujii, S.; von der Saal, W.; Zimmermann, G.; Schneider, G. Development of a virtual screening method for identification of "frequent hitters" in compound libraries J. Med. Chem. 2001, 45, 137-142
11. Hopkins, A. L.; Mason, J. S.; Overington, J. P. Can we rationally design promiscuous drugs? Curr. Opin. Struct. Biol. 2006, 16, 127-136
12. Kamal, A.; Jacques, H.; Bernard, F.; Steven, W.; Edgar, J.; Andreas, B.; Jeremy, L. J.; Laszlo, U. Modeling promiscuity based on in vitro safety pharmacology profiling data ChemMedChem 2007, 2, 874-880
13. Leeson, P. D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry Nat. Rev. Drug Discovery 2007, 6, 881-890
14. Whitlock, G. A.; Fish, P. V.; Fray, M. J.; Stobie, A.; Wakenhut, F. Pyridyl-phenyl ether monoamine reuptake inhibitors: impact of lipophilicity on dual SNRI pharmacology and off-target promiscuity Bioorg. Med. Chem. Lett. 2008, 18, 2896-2899
15. Peters, J.-U.; Schnider, P.; Mattei, P.; Kansy, M. Pharmacological promiscuity: dependence on compound properties and target specificity in a set of recent roche compounds ChemMedChem 2009, 4, 680-686
16. Bemis, G. W.; Murcko, M. A. The properties of known drugs. 1. Molecular frameworks J. Med. Chem. 1996, 39, 2887-2893
17. Bemis, G. W.; Murcko, M. A. Properties of known drugs. 2. Side chains J. Med. Chem. 1999, 42, 5095-5099
18. Xu, Y.-J.; Johnson, M. Algorithm for naming molecular equivalence classes represented by labeled pseudographs J. Chem. Inf. Comput. Sci. 2001, 41, 181-185
19. Xu, Y.-J.; Johnson, M. Using molecular equivalence numbers to visually explore structural features that distinguish chemical libraries J. Chem. Inf. Comput. Sci. 2002, 42, 912-926
20. Pipeline Pilot, version 7.5; Accelrys: San Diego, CA.
21. ClogP, version 4.3; BioByte Corp.: Claremont, CA.
22. OEChem, version 1.3.4; OpenEye Scientific Software, Inc.: Santa Fe, NM.
23. Krejsa, C. M.; Horvath, D.; Rogalski, S. L.; Penzotti, J. E.; Mao, B.; Barbosa, F.; Migeon, J. C. Predicting ADME properties and side effects: the BioPrint approach Curr. Opin. Drug Discovery Dev. 2003, 6, 470-80
24. Wilcoxon, F. Individual comparisons by ranking methods Biom. Bull. 1945, 1, 80-83
25. JMP, version 7; SAS Institute Inc.: Cary, NC.