InhaltsangabeList of contributors. Preface. Introduction: the case for polypharmacology Andrew L. Hopkins Part A: Polypharmacology - a safety concern in drug discovery. 1 The relevance of off-target polypharmacology Bruce D. Car 2 Screening for safety-relevant off-target activities Laszlo Urban, Steven Whitebread, Jacques Hamon, Dmitri Mikhailov and Kamal Azzaoui 2.1 Introduction. 2.2 General aspects. 2.3 Selection of off-targets. 2.4 In silico approaches to off-target profiling. 2.5 Summary and conclusions. 3 Pharmacological promiscuity and molecular properties JensUwe Peters 3.1 Introduction: pharmacological promiscuity in the history of drug discovery. 3.2 Lipophilicity. 3.3 Molecular weight. 3.4 Ionisation state. 3.5 Other molecular descriptors and structural motifs. 3.6 Implications for drug discovery. 4 Kinases as antitargets in genotoxicity Stephan Kirchner 4.1 Protein Kinases and inhibitor-binding sites. 4.2 CyclinDependent Kinases (CDKs) controlling unregulated cell proliferation. 4.3 Mitotic kinases as guardians protecting cells from aberrant chromosome segregation. 5 Activity at cardiovascular ion channels: a key issue for drug discovery Ian M. Bell, Mark T. Bilodeau and Armando A. Lagrutta 5.1 Introduction. 5.2 Screening methods. 5.3 Structural insights into the interaction between drugs and CV ion channels. 5.4 Medicinal Chemistry approaches. 5.5 Conclusion. 6 Prediction of side effects based on fingerprint profiling and data mining Jacques Migeon 6.1 Introduction to BioPrint. 6.2 The pharmacological fingerprint. 6.3 Antidepressant example. 6.4 Profile similarity at non-therapeutic targets. 6.5 Interpreting the polypharmacology profile. 6.6 Methods. 6.7 Patterns of activity. 6.8 Integrating function profile data with traditional pharmacological binding data. 6.9 Analysis of the antifungal tioconazole. 6.10 Conclusions. Part B: Polypharmacology - an opportunity for drug discovery. 7 Polypharmacological drugs - "magic shotguns" for psychiatric diseases Wesley K. Kroeze and Bryan L. Roth 7.1 Introduction. 7.2 Definition. 7.3 The discovery and extent of promiscuity among psychiatric drugs. 7.4 Why are so many psychiatric drugs promiscuous? 7.5 Conclusions. 8 Polypharmacological kinase inhibitors: new hopes for the therapy of cancer Annalisa Petrelli 8.1 Targeted therapies: a new era in the treatment of cancer. 8.2 The single-targeted therapy. 8.3 From single to multi-targeted drugs in cancer therapy. 8.4 Polypharmacology kinase inhibitors in clinical practice and under development. 8.5 Concluding remarks. 9 Polypharmacology as an emerging trend in antibacterial discovery Lynn L. Silver 9.1 Introduction. 9.2 Classical antibacterial polypharmacology. 9.3 New approaches to multi-targeted single pharmacophores. 9.4 Synthetic lethals. 9.5 Hybrid molecules. 9.6 Conclusions. 10 A "magic shotgun" perspective on anticonvulsant mechanisms Matt T. Bianchi and Kathy Chuang 10.1 Introduction. 10.2 Anticonvulsant mechanism. 10.3 Defining promiscuity. 10.4 Promiscuity: lessons from endogenous signaling. 10.5 Promiscuity: lessons from anticonvulsant electrophysiology. 10.6 Use of anticonvulsants in disorders other than epilepsy. 10.7 Experimental and theoretical support for a "Magic Shotgun" approach. 10.8 Current multi-target strategies. 10.9 Practical considerations. 10.10 Conclusion. 11 Selective Optimization of Side Activities (SOSA): a promising way for drug discovery Thierry Langer and Camille-Georges Wermuth 11.1 Introduction. 11.2 Definition and principle. 11.3 Rationale of SOSA. 11.4 Establishing the SOSA approach. 11.5 A successful example of the SOSA approach. 11.6 Other examples of SOSA switches. 11.7 Discussion. 11.8 Computer-assisted design using pharmacophores. 11.9 Conclusions. Par

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