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Informationen zum Autor KATYA TSAIOUN , PhD, is Chief Scientific Officer of Cyprotex and, previously, president and founder Apredica, which was acquired by Cyprotex. Both companies specialize in the rapid preclinical in vitro assessment of the ADME-Tox (Absorption, Distribution, Metabolism, Elimination, and Toxicity) properties of small-molecule and peptide therapeutics. STEVEN A. KATES , PhD is Vice President of Research and Development at Ischemix. He is a highly experienced chemist with over twenty years in R&D for both life science products and human therapeutics, and has advanced several compounds through drug development from early preclinical to early clinical development. He has more than 100 patents and publications, including one book. Klappentext Early ADMET explained: an integrated approach to successful drug development This practical guide provides medicinal chemists insights into the field of early ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicology), giving them a how-to for implementing early ADMET testing in their workflows, and maximizing the success of drug candidates in preclinical and clinical studies. The emphasis and themes illustrate the required collaboration and communication between team members from different specialties, such as chemists, biologists, formulators, toxicologists, and preclinical and clinical development specialists. The book demonstrates how this collaborative approach addresses long-standing productivity issues in the pharmaceutical industry, accelerates positive results, and helps improve the commercialization rate for therapeutic agents. Written by a group of experts from diverse disciplines, ADMET for Medicinal Chemists covers all key areas of the drug development process, including: Technical considerations when selecting preclinical drug candidates Guidelines for how to avoid pitfalls during drug design and discovery Proven cutting-edge approaches to preclinical studies and drug design Essential computer methods for designing molecules with desired properties Absorption and physicochemical properties of New Chemical Entities (NCE) The concepts underlying pharmacokinetics Assays for testing cardiac safety, genetic toxicity, and hepatic toxicity In vivo toxicological considerations and complying with FDA requirements Zusammenfassung Many pharmaceutical companies have dedicated groups directly interfacing with drug discovery however the scientific principles and strategies are practiced in a variety of different ways. Medicinal chemists need a guide to show them in how to implement early ADMET testing in order to improve both the speed and efficiency of their efforts. Inhaltsverzeichnis Preface xv Contributors xix 1 Introduction 1 Corinne Kay 1.1 Introduction 1 1.2 Voyage Through The Digestive System 2 1.2.1 The Mouth 3 1.2.2 The Stomach 4 1.2.3 The Small Intestine: Duodenum 7 1.2.4 The Small and Large Intestine: Jejunum, Ileum, Colon 9 1.2.5 Hepatic-Portal Vein 13 1.3 The Liver Metabolism 15 1.3.1 CYP450 (CYPs) 17 1.4 The Kidneys 21 1.4.1 Active Tubular Secretion 23 1.4.2 Passive Tubular Reabsorption 24 1.5 Conclusions 25 References 25 2 In Silico ADME/Tox Predictions 29 David Lagorce, Christelle Reynes, Anne-Claude Camproux, Maria A. Miteva, Olivier Sperandio, and Bruno O. Villoutreix 2.1 Introduction 29 2.2 Key Computer Methods for ADME/Tox Predictions 30 2.2.1 Drug Discovery 30 2.2.2 Applying or Not ADME/Tox Predictions, Divided Opinions 35 2.2.3 In Silico ADME/Tox Methods and Modeling Approaches 39 2.2.4 Physicochemistry, Pharmacokinetics, Drug-Like and Lead-Like Concepts 46 2.2.5 Lipophilicity 51
