Skip to main content
SpringerLink
Log in
Book cover

Chemogenomics pp 1–19Cite as

Organizing Bioactive Compound Discovery in Target Families

  • Protocol
  • First Online:

  • 914 Accesses

Part of the book series: Methods in Molecular Biology ((MIMB,volume 575))

Summary

The sequencing of genomes gave access to the complete set of building blocks for organisms of various species. A plethora of “-omics”-technologies has been developed to investigate the dynamic interactions of the building blocks in order to understand the functioning of living organisms. This has given rise to the clustering of proteins into target families based on the phylogenetic and structural similarities. In this chapter we will discuss how the concept of target families enables to investigate and modulate biochemical function in the quest to chart Chemical and Biological Spaces.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Lipinski, C.A., Lombardo, F., Dominy, B.W., and Feeney, P.J. (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug. Deliv. Rev. 23, 3–25.

    Article  CAS  Google Scholar 

  2. Veber, D.F., Johnson, S.R., Cheng, H.-Y., Smith, B.R., Ward, K.W., and Kopple, K.D. (2002) Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 45, 2615–2623.

    Article  PubMed  CAS  Google Scholar 

  3. Venter, J.C., Adams, M.D., Myers, E.W., et al. (2001) The sequence of the human genome. Science 291, 1304–1351.

    Article  PubMed  CAS  Google Scholar 

  4. Drews, J. (2000) Drug discovery: A historical perspective. Science 287, 1960–1963.

    Article  PubMed  CAS  Google Scholar 

  5. Hopkins, A.L, and Groom, C.R. (2002) The druggable genome. Nat. Rev. Drug Discov. 1, 727–730.

    Article  PubMed  CAS  Google Scholar 

  6. Overington, J.P., Al-Lazikani, B., and Hopkins, A.L. (2006) How many drug targets are there? Nat. Rev. Drug. Discov. 5, 993–996.

    Article  PubMed  CAS  Google Scholar 

  7. Russ, A.P., and Lampel, S. (2005) The druggable genome: An update. Drug. Discov. Today 10, 1607–1610.

    Article  PubMed  Google Scholar 

  8. Hajduk, P.J., Huth, J.R., and Tse, C. (2005) Predicting protein druggability. Drug Discov. Today 10, 1675–1682.

    Article  PubMed  CAS  Google Scholar 

  9. Paolini, G.V., Shapland, R.H.B., van Hoorn, W.P., Mason, J.S., and Hopkins, A.L. (2006) Global mapping of pharmacological space. Nat. Biotechnol. 24, 805–815.

    Article  PubMed  CAS  Google Scholar 

  10. Narayanan, V.K., Douglas, F., Schirlin, D., Wess, G., and Giesing, D. (2004) Virtual commu­nities as an organizational mechanism for embedding knowledge in drug discovery: The case of chemical biology platform. J. Business Chem. 1, 37–47.

    Google Scholar 

  11. Douglas, F.L. (2007) Managerial challenges in implementing chemical biology platforms. In: Schreiber, S.L., Kapoor, T.M., and Wess, G. (eds.) Chemical Biology: From Small Molecules to Systems Biology and Drug Design. Wiley-VCH, Weinheim, pp. 789–803.

    Chapter  Google Scholar 

  12. Palczewski, K., Kumasaka, T., Hori, T., et al. (2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289, 739–745.

    Article  PubMed  CAS  Google Scholar 

  13. Jiang, Y., Lee, A., Chen, J., Cadene, M., Chait, B.T., and MacKinnon, R. (2002) Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417, 515–522.

    Article  PubMed  CAS  Google Scholar 

  14. Nishida, M., and MacKinnon, R. (2002) Stru­ctural basis of inward rectification: Cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8.ANG. resolution. Cell 111, 957–965.

    Article  PubMed  CAS  Google Scholar 

  15. Eschenmoser, A. (1994) One hundred years of the lock-and-key principle. Angew. Chem. Int. Ed. Engl. 33, 2363.

    Article  Google Scholar 

  16. Woodward, R.B. (1972) Recent advances in the chemistry of natural products (Nobel Lecture, December 11, 1965). In: Nobel Foundation (ed.) Nobel Lectures, Chemistry 1963–1970. Elsevier, Amsterdam, pp. 100–121.

    Google Scholar 

  17. Corey, E.J. (1991) The logic of chemical synthesis: Multistep synthesis of complex carbogenic molecules. (Nobel lecture). Angew. Chem. Int. Ed. Engl. 30, 455–465.

    Article  Google Scholar 

  18. Bohacek, R.S., McMartin, C., and Guida, W.C. (1996) The art and practice of structure-based drug design: A molecular modeling perspective. Med. Res. Rev. 16, 3–50.

    Article  PubMed  CAS  Google Scholar 

  19. Bemis, G.W., and Murcko, M.A. (1996) The properties of known drugs. 1. Molecular frameworks. J. Med. Chem. 39, 2887–2893.

    Article  PubMed  CAS  Google Scholar 

  20. Bondensgaard, K., Ankersen, M., Thogersen, H., Hansen, B.S., Wulff, B.S., and Bywater, R.P. (2004) Recognition of privileged structures by G-protein coupled receptors. J. Med. Chem. 47, 888–899.

    Article  PubMed  CAS  Google Scholar 

  21. Vieth, M., Higgs, R.E., Robertson, D.H., Shapiro, M., Gragg, E.A., and Hemmerle, H. (2004) Kinomics-structural biology and chemogenomics of kinase inhibitors and targets. Biochim. Biophys. Acta 1697, 243–257.

    Article  PubMed  CAS  Google Scholar 

  22. Chiang, R.A., Sali, A., and Babbitt, P.C. (2008) Evolutionarily conserved substrate substructures for automated annotation of enzyme superfamilies. PLoS Comput. Biol. 4, e1000142.

    Article  PubMed  Google Scholar 

  23. Fliri, A.F., Loging, W.T., Thadeio, P.F., and Volkmann, R.A. (2005) Biospectra analysis: Model proteome characterizations for linking molecular structure and biological response. J. Med. Chem. 48, 6918–6925.

    Article  PubMed  CAS  Google Scholar 

  24. Fliri, A.F., Loging, W.T., Thadelo, P.F., and Volkmann, R.A. (2005) Biological spectra analysis: Linking biological activity profile to molecular structure. Proc. Natl. Acad. Sci. U.S.A. 102, 261–265.

    Article  PubMed  CAS  Google Scholar 

  25. Bender, A., Young, D.W., Jenkins, J.L., ­Serrano, M., Mikhailov, D., Clemons, P.A., and Davies, J.W. (2007) Chemogenomic data analysis: Prediction of small-molecule targets and the advent of biological fingerprints. Comb. Chem. High Throughput Screen. 10, 719–731.

    Article  PubMed  CAS  Google Scholar 

  26. Bajorath, J. (2008) Computational analysis of ligand relationships within target families. Curr. Opin. Chem. Biol. 12, 352–358.

    Article  PubMed  CAS  Google Scholar 

  27. Naumann, T., and Matter, H. (2002) Structural classification of protein kinases using 3D molecular interaction field analysis of their ligand binding sites: Target family landscapes. J. Med. Chem. 45, 2366–2378.

    Article  PubMed  CAS  Google Scholar 

  28. Matter, H., and Schwab, W. (1999) Affinity and selectivity of matrix metalloproteinase inhibitors: A chemometrical study from the perspective of ligands and proteins. J. Med. Chem. 42, 4506–4523.

    Article  PubMed  CAS  Google Scholar 

  29. Klabunde, T. (2007) Chemogenomic appro­aches to drug discovery: Similar receptors bind similar ligands. Br. J. Pharmacol. 152, 5–7.

    Article  PubMed  CAS  Google Scholar 

  30. Klabunde, T., and Hessler, G. (2002) Drug design strategies for targeting G-protein-coupled receptors. ChemBioChem 3, 928–944.

    Article  PubMed  CAS  Google Scholar 

  31. Radestock, S., Weil, T., and Renner, S. (2008) Homology model-based virtual screening for GPCR ligands using docking and target-biased scoring. J. Chem. Inf. Model. 48, 1104–1117.

    Article  PubMed  CAS  Google Scholar 

  32. Hummel, P., Vaidehi, N., Floriano, W.B., Hall, S.E., and Goddard, W.A. III. (2005) Test of the binding threshold hypothesis for olfactory receptors: Explanation of the differential binding of ketones to the mouse and human orthologs of olfactory receptor 912–93. Protein Sci. 14, 703–710.

    Article  PubMed  CAS  Google Scholar 

  33. Shacham, S., Marantz, Y., Bar-Haim, S., Kalid, O., Warshaviak, D., Avisar, N., Inbal, B., Heifetz, A., Fichman, M., Topf, M., Naor, Z., Noiman, S., and Becker, O.M. (2004) PREDICT modeling and in-silico screening for G-protein coupled receptors. Proteins 57, 51–86.

    Article  PubMed  CAS  Google Scholar 

  34. Becker, O.M., Marantz, Y., Shacham, S., Inbal, B., Heifetz, A., Kalid, O., Bar-Haim, S., Warshaviak, D., Fichman, M., and Noiman, S. (2004) G protein-coupled receptors: In silico drug discovery in 3D. Proc. Natl. Acad. Sci. U.S.A. 101, 11304–11309.

    Article  PubMed  CAS  Google Scholar 

  35. Rosenbaum, D.M., Cherezov, V., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Yao, X.J., Weis, W.I., Stevens, R.C., and Kobilka, B.K. (2007) GPCR engineering yields high-resolution structural insights into beta 2-adrenergic receptor function. Science 318, 1266–1273.

    Article  PubMed  CAS  Google Scholar 

  36. Cherezov, V., Rosenbaum, D.M., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Kuhn, P., Weis, W.I., Kobilka, B.K., and Stevens, R.C. (2007) High-resolution crystal structure of an engineered human beta 2-adrenergic G protein-coupled receptor. Science 318, 1258–1265.

    Article  PubMed  CAS  Google Scholar 

  37. Rasmussen, S.G., Choi, H.J., Rosenbaum, D.M., Kobilka, T.S., Thian, F.S., Edwards, P.C., Burghammer, M., Ratnala, V.R., Sanishvili, R., Fischetti, R.F., Schertler, G.F., Weis, W.I., and Kobilka, B.K. (2007) Crystal structure of the human beta 2 adrenergic G-protein-coupled receptor. Nature 450, 383–387.

    Article  PubMed  CAS  Google Scholar 

  38. Jacoby, E., Bouhelal, R., Gerspacher, M., and Seuwen, K. (2006) The 7 TM G-protein-coupled receptor target family. ChemMedChem 1, 760–82.

    Article  CAS  Google Scholar 

  39. Civelli, O. (2005) GPCR deorphanizations: The novel, the known and the unexpected transmitters. Trends Pharmacol. Sci. 26, 15–19.

    Article  PubMed  CAS  Google Scholar 

  40. Chung, S., Funakoshi, T., and Civelli, O. (2007) Orphan GPCR research. Br. J. Pharmacol. 153(S1), S339–S346.

    Article  PubMed  Google Scholar 

  41. Levoye, A., and Jockers, R. (2008) Alternative drug discovery approaches for orphan GPCRs. Drug Discov. Today 13, 52–58.

    Article  PubMed  CAS  Google Scholar 

  42. Hou, Y., Felsch, J., Annis, A., et al. (2002) Identification of Small Molecule Ligands for G Protein Coupled Receptor Using Affinity Selection Screening. GPCR IBC Conference 2002.

    Google Scholar 

  43. Martin, Y.C., Kofron, J.L., and Traphagen, L.M. (2002) Do structurally similar molecules have similar biological activity? J. Med. Chem. 45, 4350–4358.

    Article  PubMed  CAS  Google Scholar 

  44. Aronov, A.M., McClain, B., Moody, C.S., and Murcko, M.A. (2008) Kinase-likeness and kinase-privileged fragments: Toward virtual polypharmacology. J. Med. Chem. 51, 1214–1222.

    Article  PubMed  CAS  Google Scholar 

  45. Aronov, A.M., and Murcko, M.A. (2004) Toward a pharmacophore for kinase frequent hitters. J. Med. Chem. 47, 5616–5619.

    Article  PubMed  CAS  Google Scholar 

  46. Fabian, M.A., Biggs, W.H., Treiber, D.K., et al. (2005) A small molecule-kinase interaction map for clinical kinase inhibitors. Nat. Biotechnol. 23, 329–336.

    Article  PubMed  CAS  Google Scholar 

  47. Free, S.M., and Wilson, J.W. (1964) A mathematical contribution to structure-activity relationships. J. Med. Chem. 7, 395–399.

    Article  PubMed  CAS  Google Scholar 

  48. Sciabola, S., Stanton, R.V., Wittkopp, S., et al. (2008) Predicting kinase selectivity profiles using Free-Wilson QSAR analysis. J. Chem. Inf. Model. 48, 1851–1867.

    Article  PubMed  CAS  Google Scholar 

  49. Dunayevskiy, Y.M., Vouros, P., Wintner, E.A., Shipps, G.W., Carell, T., and Rebek, J. Jr. (1996) Application of capillary electrophoresis-electrospray ionization mass spectrometry in the determination of molecular diversity. Proc. Natl. Acad. Sci. U.S.A. 93, 6152–6157.

    Article  PubMed  CAS  Google Scholar 

  50. Agnihotri, G., Scott, M.P., Alaoui-Ismaili, M.H., et al. (2004) Identification of Potent Inhibitors of c-Jun N-terminal Kinase-1 (JNK1) using Ultra High-Throughput Affinity Based Screening. 12th Symposium on Second Messengers and Phospho-proteins (SMP-2004).

    Google Scholar 

  51. Hartshorn, M.J., Murray, C.W., Cleasby, A., ­Frederickson, M., Tickle, I.J., and Jhoti, H. (2005) Fragment-based lead discovery using X-ray crystallography. J. Med. Chem. 48, 403–413.

    Article  PubMed  CAS  Google Scholar 

  52. Congreve, M.S., Davis, D.J., Devine, L., et al. (2003) Detection of ligands from a dynamic combinatorial library by X-ray crystallography. Angew. Chem. Int. Ed. Engl. 42, 4479–4482.

    Article  PubMed  CAS  Google Scholar 

  53. Hajduk, P.J., Bures, M., Praestgaard, J., and Fesik, S.W. (2000) Privileged molecules for protein binding identified from NMR-based screening. J. Med. Chem. 43, 3443–3447.

    Article  PubMed  CAS  Google Scholar 

  54. Hajduk, P.J., Gomtsyan, A., Didomenico, S., et al. (2000) Design of adenosine kinase inhibitors from the NMR-based screening of fragments. J. Med. Chem. 43, 4781–4786.

    Article  PubMed  CAS  Google Scholar 

  55. Nestler, H.P. (2005) Combinatorial chemistry and fragment screening - two unlike siblings? Curr. Drug Discov. Technol. 2, 1–12.

    Article  PubMed  CAS  Google Scholar 

  56. Congreve, M., Chessari, G., Tisi, D., and Woodhead, A.J. Recent developments in fragment-based drug discovery. J. Med. Chem. 51, 3661–3680.

    Google Scholar 

  57. Degen, J., Wegscheid-Gerlach, C., Zaliani, A., and Rarey, M. (2008) On the art of compiling and using ‘drug-like’ chemical fragment spaces. ChemMedChem. 3, 1503–1507.

    Article  PubMed  CAS  Google Scholar 

  58. Greenbaum, D.C., Arnold, W.D., Lu, F., et al. (2002) Small molecule affinity fingerprinting a tool for enzyme family subclassification, target identification, and inhibitor design. Chem. Biol. 9, 1085–1094.

    Article  PubMed  CAS  Google Scholar 

  59. Greenbaum, D., Baruch, A., Hayrapetian, L., Darula, Z., Burlingame, A., Medzihradszky, K.F., and Bogyo, M. (2002) Chemical approaches for functionally probing the proteome. Mol. Cell. Proteomics 1, 60–68.

    Article  PubMed  CAS  Google Scholar 

  60. Blum, G., Degenfeld, G.V., Merchant, M.J., Blau, H.M., and Bogyo, M. (2007) Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat. Chem. Biol. 3, 668–677.

    Article  PubMed  CAS  Google Scholar 

  61. Zacharakis, G., Kambara, H., Shih, H., Ripoll, J., Grimm, J., Saeki, Y., Weissleder, R., and Ntziachristos, V. (2005) Volumetric tomography of fluorescent proteins through small animals in vivo. Proc. Natl. Acad. Sci. U.S.A. 102, 18252–18257.

    Article  PubMed  CAS  Google Scholar 

  62. Jaffer, F.A., Tung, C.H., Gerszten, R.E., and Weissleder, R. (2002) In vivo imaging of thrombin activity in experimental thrombi with thrombin-sensitive near-infrared molecular probe. Arterioscler. Thromb. Vasc. Biol. 22, 1929–1935.

    Article  PubMed  CAS  Google Scholar 

  63. Mahmood, U., Tung, C.H., Bogdanov, A. Jr., and Weissleder, R. (1999) Near-infrared optical imaging of protease activity for tumor detection. Radiology 213, 866–870.

    PubMed  CAS  Google Scholar 

  64. Watzke, A., Kosec, G., Kindermann, M., et al. (2008) Selective activity-based probes for cysteine cathepsins. Angew. Chem. Int. Ed. Engl. 47, 406–409.

    Article  PubMed  CAS  Google Scholar 

  65. Bredemeyer, A.J., Lewis, R.M., Malone, J.P., et al. (2004) A proteomic approach for the discovery of protease substrates. Proc. Natl. Acad. Sci. U.S.A. 101, 11785–11790.

    Article  PubMed  CAS  Google Scholar 

  66. Nestler, H.P. and Doseff, A. (1997) A two-dimensional, diagonal sodium dodecyl sulfate polyacrylamide gel electrophoresis technique to screen for protease substrates in protein mixtures. Anal. Biochem. 251, 122–125.

    Article  PubMed  CAS  Google Scholar 

  67. St. Hilaire, P.M., Willert, M., Juliano, M.A., Juliano, L., and Meldal, M. (1999) Fluorescence-quenched solid phase combinatorial libraries in the characterization of cysteine protease substrate specificity. J. Comb. Chem. 1, 509–523.

    Article  PubMed  CAS  Google Scholar 

  68. Meldal, M. (2002) The one-bead two-compound assay for solid phase screening of combinatorial libraries. Biopolymers 66, 93–100.

    Article  PubMed  CAS  Google Scholar 

  69. Tyndall, J.D.A., Nall, T., and Fairlie, D.P. (2005) Proteases universally recognize beta strands in their active sites. Chem. Rev. 105, 973–999.

    Article  PubMed  CAS  Google Scholar 

  70. Leung, D., Abbenante, G., and Fairlie, D.P. (2000) Protease inhibitors: Current status and future prospects. J. Med. Chem. 43, 305–341.

    Article  PubMed  CAS  Google Scholar 

  71. Hajduk, P.J., Sheppard, G., Nettesheim, D.G., et al. (1997) Discovery of potent nonpeptide inhibitors of stromelysin using SAR by NMR. J. Am. Chem. Soc. 119, 5818–5827.

    Article  CAS  Google Scholar 

  72. Olejniczak, E.T., Hajduk, P.J., Marcotte, P.A., et al. (1997) Stromelysin inhibitors designed from weakly bound fragments: Effects of linking and cooperativity. J. Am. Chem. Soc. 119, 5828–5832.

    Article  CAS  Google Scholar 

  73. Hajduk, P.J., Boyd, S., Nettesheim, D., et al. (2000) Identification of novel inhibitors of urokinase via NMR-based screening. J. Med. Chem. 43, 3862–3866.

    Article  PubMed  CAS  Google Scholar 

  74. Wendt, M.D., Rockway, T.W., Geyer, A., et al. (2004) Identification of novel binding interactions in the development of potent, selective 2-naphthamidine inhibitors of urokinase. Synthesis, structural analysis, and SAR of N-phenyl amide 6-substitution. J. Med. Chem. 47, 303–324.

    Article  PubMed  CAS  Google Scholar 

  75. Metz, G., Ottleben, H., and Vetter, D. (2003) Small molecule screening on chemical microarrays. In: Böhm, H.J., and Schneider, G. (eds.) Protein-Ligand Interactions, From Molecular Recognition to Drug Design. Wiley-VCH, Weinheim, pp. 213–236.

    Google Scholar 

  76. Dickopf, S., Frank, M., Junker, H.D., et al. (2004) Custom chemical microarray production and affinity fingerprinting for the S1 pocket of factor VIIa. Anal. Biochem. 335, 50–57.

    Article  PubMed  CAS  Google Scholar 

  77. Mitcheson, J.S., Chen, J., Lin, M., Culberson, C., and Sanguinetti, M.C. (2000) A structural basis for drug-induced long QT-syndrome. Proc. Natl. Acad. Sci. U.S.A. 97, 12329–12333.

    Article  PubMed  CAS  Google Scholar 

  78. Haverkamp, W., Breithardt, G., Camm, A.J., et al. (2000) The potential for QT prolongation and proarrhythmia by non-antiarrhythmic drugs: Clinical and regulatory implications. Report on a Policy Conference of the European Society of Cardiology. Eur. Heart J. 21, 1216–1231.

    Article  PubMed  CAS  Google Scholar 

  79. Kuo, A., Gulbis, J.M., Antcliff, J.F., et al. (2003) Crystal structure of the potassium channel KirBac1.1 in the closed state. Science 300, 1922–1926.

    Article  PubMed  CAS  Google Scholar 

  80. Pearlstein, R.A., Vaz, R.J., Kang, J., et al. (2003) Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches. Bioorg. Med. Chem. Lett. 13, 1829–1835.

    Article  PubMed  CAS  Google Scholar 

  81. Aronov, A.M. (2005) Predictive in silico modeling for hERG channel blockers. Drug Discov. Today 10, 149–155.

    Article  PubMed  CAS  Google Scholar 

  82. Antcliff, J.F., Haider, S., Proks, P., Sansom, M.S.P., and Ashcroft, F.M. Functional analysis of a structural model of the ATP-binding site of the KATP channel Kir6.2 subunit. EMBO J. 24, 229–239.

    Google Scholar 

  83. Jensen, B.F., Vind, C., Padkjar, S.B., Brockhoff, P.B., and Refsgaard, H.H.F. In silico prediction of cytochrome P450 2D6 and 3A4 inhibition using gaussian kernel weighted k-nearest neighbor and extended connectivity fingerprints, including structural fragment analysis of inhibitors versus noninhibitors. J. Med. Chem. 50, 501–511.

    Google Scholar 

  84. Kontijevskis, A., Komorowski, J., and Wikberg, J.E. (2008) Generalized proteochemometric model of multiple cytochrome p450 enzymes and their inhibitors. J. Chem. Inf. Model. 48, 1840–1850; PMID: 18693719.

    Article  PubMed  CAS  Google Scholar 

  85. Gleeson, M.P. (2008) Generation of a set of simple, interpretable ADMET rules of thumb. J. Med. Chem. 51, 817–834.

    Article  PubMed  CAS  Google Scholar 

  86. Wess, G., Urmann, M., and Sickenberger, B. (2001) Medicinal chemistry: Challenges and opportunities. Angew. Chem. Int. Ed. Engl. 40, 3341–3350.

    Article  PubMed  CAS  Google Scholar 

  87. Mueller, G. (2003) Medicinal chemistry of target family-directed masterkeys. Drug Discov. Today 8, 681–691.

    Article  CAS  Google Scholar 

  88. Nestler, H.P. (2007) The target family approach. In: Schreiber, S.L., Kapoor, T., Wess, G. (eds.) Chemical Biology: From Small Molecules to Systems Biology and Drug Design. 1. Wiley-VCH, Weinheim, pp. 825–851.

    Google Scholar 

  89. Fischer, E. (1894) Effekt der Zuckerkonfiguration auf die Enzymwirkung. Berichte 27, 2984–2993.

    Google Scholar 

  90. Koshland, D.E. Jr. (1994) The lock-and-key principle and the induced-fit theory. Angew. Chem. Int. Ed. Engl. 33, 2475–2478.

    Google Scholar 

  91. Horrobin, D.F. (2003) Opinion: Modern biomedical research: An internally self-consistent universe with little contact with medical reality? Nat. Rev. Drug Discov. 2, 151–154.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sanofi-Aventis Combinatorial Technologies Center, Tucson, AZ, USA

    H. Peter Nestler

Authors
  1. H. Peter Nestler
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Spiegelbergstr. 29, Basel, 4059, Switzerland

    Edgar Jacoby

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Nestler, H.P. (2009). Organizing Bioactive Compound Discovery in Target Families. In: Jacoby, E. (eds) Chemogenomics. Methods in Molecular Biology, vol 575. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-274-2_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-274-2_1

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-273-5

  • Online ISBN: 978-1-60761-274-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation