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Informationen zum Autor Jens-Uwe Peters, PhD, works in the Medicinal Chemistry Department at F. Hoffmann-La Roche. In his ten years at Roche, he has been involved in numerous drug discovery projects, has contributed to Early Safety Profiling initiatives, and has researched opportunities for polypharmacological drug discovery. Dr. Peters is author or coauthor on twenty-six journal papers and is named on twenty-two patents. Klappentext An essential outline of the main facets of polypharmacology in drug discovery researchExtending drug discovery opportunities beyond the "one drug, one target" philosophy, a polypharmacological approach to the treatment of complex diseases is emerging as a hot topic in both industry and academic research. Polypharmacology in Drug Discovery presents an overview of the various facets of polypharmacology and how it can be applied as an innovative concept for developing medicines for treating bacterial infections, epilepsy, cancer, psychiatric disorders, and more. Filled with a collection of instructive case studies that reinforce the material and illuminate the subject, this practical guide:* Covers the two-sided nature of polypharmacology-its contribution to adverse drug reactions and its benefit in certain therapeutic drug classes* Addresses the important topic of polypharmacology in drug discovery, a subject that has not been thoroughly covered outside of scattered journal articles* Overviews state-of-the-art approaches and developments to help readers understand concepts and issues related to polypharmacology* Fosters interdisciplinary drug discovery research by embracing computational, synthetic, in vitro and in vivo pharmacological and clinical aspects of polypharmacologyA clear road map for helping readers successfully navigate around the problems involved with promiscuous ligands and targets, Polypharmacology in Drug Discovery provides real examples, in-depth explanations and discussions, and detailed reviews and opinions to spark inspiration for new drug discovery projects. Zusammenfassung Polypharmacology can be the two-faced Janus in drug discovery and pharmacology: an adverse, off-target safety risk in some cases or a necessity for effectively treating complex diseases like psychosis and cancer. Inhaltsverzeichnis List 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 Jens-Uwe 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 Cyclin-Dependent 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 Medic...
