Ligand-based Lead Finding

For similarity searching, all molecules are described by an appropriate binary descriptor (consisting of only zeros and ones). Such a binary fingerprint contains all structural information for a particular molecule and was applied at Aventis to identify new Kvl.5 inhibitors in the compound collection. 

this recent example nicely demonstrates that ion channel ligands can be valuable starting points for the identification of drugs acting against other members of the ion channel protein family. 

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Distinguishing Molecules of Different Biol< ical Activities and Finding a New Lead Structure - An Example of Ligand-Based Drug Design... 

The concept of drug development is based on the findings that retinoid receptors (RARs and RXRs) offer a new approach by targeting different genes depending on the activated retinoid receptor complexes. The multiplicity of these retinoid signaling pathways affords potential for therapeutic opportunity as well as retinoid therapy associated undesired side effects. It is possible that the indiscriminate activation of all pathways by nonspecific retinoid ligands could lead to unacceptable side effects so that any enhanced efficacy would be obtained at the cost of enhanced toxicity. 

The editors would like to thank the contributors to this volume for their cooperation. We are sure that scientists entering the field of structure-based ligand design will find in this volume the adequate support for the successful application of lead discovery techniques. 

R 151 G.C.K. Roberts, The Determination of Equilibrium Dissociation Constants of Protein-Ligand Complexes by NMR , p. 309 R 152 C. Marchioro, S. Davalli, S. Provera, M. Heller, A. Ross and H. Senn, Experiments in NMR-Based Screening , p. 321 R 153 W. Jahnke, The Use of Spin Labels in NMR-Supported Lead Finding and Optimization , p. 341... 

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