“However, anyone interested in the complex issues relating to drug promiscuity should find this very timely and topical book to be a reliable and stimulating reference that they will revisit many times.” (ChemMedChem, 2012)
Polypharmacology in Drug Discoveryby Jens-Uwe Peters
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. This book overviews these facets of polypharmacology to help drug discovery researchers both address adverse polypharmacology and approach the… See more details below
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. This book overviews these facets of polypharmacology to help drug discovery researchers both address adverse polypharmacology and approach the discovery of polypharmacological drugs, with a third section of the book uses selected case studies to illustrate drug discovery opportunities. This resource fosters interdisciplinary drug discovery research by guiding researchers in neighboring areas to polypharmacology.
Description: This book examines the emerging polypharmacological philosophy in drug discovery research (a single compound with multiple targets), challenging the current "one-drug-one-target" approach to drug discovery. It reviews the necessary considerations during safety profiling to assess the delicate balance between promiscuous drugs' therapeutic efficacies (benefits) and adverse drug reactions, or ADRs (risks).
Purpose: Historically, researchers have sought to develop highly selective drugs in an effort to minimize ADRs due to unintended off-target effects. However, this book educates readers about the unique advantages that polypharmacological therapies have over single-target compounds, particularly in treating complex disease states, where either multiple factors contribute to pathogenicity or drug resistance arises.
Audience: This book is intended to guide drug development researchers in academic and industry sectors alike through the inherent challenges of the polypharmacological approach, with in-depth discussion of the benefits and dangers of promiscuous ligands and targets. Additionally, as the chapters of this book are authored by highly qualified experts in the pharmaceutical sciences, pharmacology students will benefit from the discussion of the fundamental concepts of polypharmacology.
Features: Organized into four distinct sections, the book begins with a discussion of the safety concerns due to off-target activities, as well as rationale for considering these activities early in the drug discovery process. The next section describes the advantages of a polypharmacological approach to drug development over a single-target philosophy by targeting networks of disease-related pathways, citing therapies for psychiatric diseases, cancer, bacterial infections, and epilepsy. The third section reviews state-of-the-art interdisciplinary approaches to promiscuous drug development that combine computational modeling with in vitro and in vivo screening assays. Finally, the last section contains various case studies with real examples of currently marketed multitargeted compounds that modulate diverse networks in the treatment of complex, polygenic diseases.
Assessment: To date, the discussion surrounding polypharmacology has been limited to a small number of journal articles and a single chapter in Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs, Barratt and Frail Wiley-Blackwell, 2012). This book is a unique and comprehensive resource for navigating the field of promiscuous drug development and research.
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