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ÊéÃûAntitargets and Drug Safety ×÷ÕßL¨¢szl¨® Urb¨¢n, Vinod F. Patel, and Roy J. Vaz ³ö°æÉç wiley Ò³Êý527 Print ISBN: 978-3-527-33511-4 ePDF ISBN: 978-3-527-67367-4 ePub ISBN: 978-3-527-67366-7 Mobi ISBN: 978-3-527-67365-0 oBook ISBN: 978-3-527-67364-3Contents List of Contributors XV Preface XXI A Personal Foreword XXIII Section 1 General Concept for Target-based Safety Assessment 1 1 Side Effects of Marketed Drugs: The Utility and Pitfalls of Pharmacovigilance 3 Steven Whitebread, Mateusz Maciejewski, Alexander Fekete, Eugen Lounkine, and L¨¢szl¨® Urb¨¢n 1.1 Introduction 3 1.2 Postmarketing Pharmacovigilance 6 1.3 Polypharmacy and Pharmacological Promiscuity of Marketed Drugs 9 References 15 2 In Silico Prediction of Drug Side Effects 19 Michael J. Keiser 2.1 Large-Scale Prediction of Drug Activity 20 2.1.1 Networks of Known and New Target Activity 21 2.1.1.1 Predicting Drug Off-Targets by Statistical Chemical Similarity 21 2.1.1.2 Representing Drugs Computationally for Rapid Comparison 23 2.1.2 Resources for Multiscale Inquiry 25 2.1.2.1 Ligands to Targets 25 2.1.2.2 Perturbing Biological Systems (Phenotypes) 25 2.1.2.3 Functional and Biological Annotations (Diseases) 27 2.1.2.4 Adverse Reactions as Drug-Induced Diseases 29 2.2 Multiscale Models of Adverse Drug Reactions 30 2.2.1 Inferring Adverse Reactions 31 2.2.1.1 From Off-Targets to Antitargets 31 2.2.1.2 Systematic Antitarget Prediction and Testing 32 2.2.1.3 Finding Side Effects sans Targets 33 2.2.2 Forward Perturbation and Prediction of Mechanisms 33 |
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