Gerhard Ecker is Full Professor for Pharmacoinformatics at the Department of Pharmaceutical Chemistry, University of Vienna (Austria). His main scientific interests are pharmacoinformatic approaches to target drug transporters, in silico screening methods for promiscuous targets and antitargets, and new approaches for data integration and data mining. Rasmus Pr?torius Clausen is Associate Professor at Dept. Drug Design and Pharmacology, University of Copenhagen (former Royal School of Pharmacy) where he also did post-doctoral studies with P. Krogsgaard-Larsen. His main research topics are neuromedicinal chemistry with focus on glutamate, GABA and GHB, and epigenetic medicinal chemistry. He has a M.Sc. degree from University of Southern Denmark (Chemistry/Cell Biology) and a PhD degree from the University of Aarhus (Denmark). Harald Sitte studied Medicine at the Universities of Innsbruck and Vienna (Austria). He was appointed Professor for Psychopharmacology at Vienna Medical University in 2010. His main scientific research interests are the structure-function relationships in neurotransmitter transporters and the pharmacological activity of psychopharmacological medicines and drugs of abuse.

• Preface XIIIA Personal Foreword XVII1 Insights into Transporter Classifications: an Outline of Transporters as Drug Targets 1Michael Viereck, Anna Gaulton, and Daniela Digles1.1 Introduction 11.2 Available Transporter Classifications 21.3 Function versus Sequence Similarity 71.4 Merged Top-Level Transporter Classification 71.5 Choice and Design of the New ChEMBL Classification 111.6 Transporter as Drug Targets 121.7 Drug Targets in the SLC Classification 151.8 Conclusions 17Acknowledgment 17References 182 New Trends in Antidepressant Drug Research 21Benny Bang-Andersen, Klaus P. Bøgesø, Jan Kehler, and Connie Sánchez2.1 Introduction 212.2 Reuptake Blockers 262.3 Multimodal Drugs 362.4 Conclusions 42List of Abbreviations 42References 433 The Molecular Basis of the Interaction Between Drugs and Neurotransmitter Transporters 53Harald H. Sitte, Thomas Stockner, and Michael Freissmuth3.1 Introduction 533.2 Crystal Structures of SLC6 Transporters 553.3 The Binding Site Proper 603.4 The Transport Cycle 613.5 Conclusions and Perspectives 63Acknowledgments 64References 644 γ-Aminobutyric Acid and Glycine Neurotransmitter Transporters 69Petrine Wellendorph, Julie Jacobsen, Jonas Skovgaard-Petersen, Andreas Jurik, Stine B. Vogensen, Gerhard Ecker, Arne Schousboe, Povl Krogsgaard-Larsen, and Rasmus P. Clausen4.1 Introduction 694.2 GABA Transporters 734.3 Glycine Transporters 904.4 Conclusions and Future Perspectives 95References 965 ABC Transporters: From Targets to Antitargets and Back 107Gerhard F. Ecker5.1 Introduction 1075.2 ABC Transporter as Drug Targets 1095.3 ABC Transporter: from Targets to Antitargets 1115.4 Pharmacochaperones and Beyond 1135.5 Conclusions and Outlook 114Acknowledgment 115References 1156 ABC Transporters Involved in Cholestasis 119Frans J. C. Cuperus, Julien Gautherot, Emina Halilbasic, Thierry Claudel, and Michael Trauner6.1 Introduction 1196.2 Canalicular ABC Transporters 1226.3 Basolateral ABC Transporters 1366.4 Nuclear Receptors as Drug Targets 1406.5 Ursodeoxycholic Acid Treatment in Cholestatic Liver Disease 1446.6 Conclusions 145References 1457 Recent Advances in Structural Modeling of ABC Transporters 167Dennis Haake, Peter Chiba, and Gerhard F. Ecker7.1 Introduction 1677.2 ABC Transporter Modeling Attempts Since 2001 1687.3 Retraction of Five Transporter Structures 1707.4 First Mammalian ABC Transporter Structure 1737.5 Conclusions and Perspectives 175Acknowledgment 175References 1758 PET Imaging of ABC Transporters at the Blood–Brain Barrier 179Oliver Langer8.1 The Blood–Brain Barrier 1798.2 The Brain as a Pharmacological Sanctuary 1808.3 Implication of ABC Transporters in Neurological Disorders 1808.4 Positron Emission Tomography 1818.5 PET Imaging of ABC Transporters 1818.6 Challenges in Designing PET Tracers for ABC Transporters 1848.7 Potential Applications of PET Tracers for ABC Transporters 1848.8 Overview of Available PET Tracers for Cerebral ABC Transporters 1858.9 Summary 191Abbreviations 191References 1919 The Systems Biology of Transporters – Targeting the Regulatory System for Transporters (FXR/RXR) 199Antimo Gioiello, Maura Marinozzi, Bruno Cerra, Chiara Custodi, Roberto Pellicciari, and Antonio Macchiarulo9.1 Introduction 1999.2 Discovery and Pharmacological Characterization of FXR 2009.3 Regulation of the Hepatobiliary Transport System by FXR 2019.4 Genetic and Structural Properties of FXR 2079.5 FXR Ligands 2099.6 Conclusions and Perspectives 221References 22110 ANO1 as a Novel Drug Target 231Anke Bill and Larry Alex Gaither10.1 Introduction 23110.2 ANO1: a Calcium Activated Chloride Channel 23210.3 Pharmacological Targeting of ANO1 23810.4 ANO1 as a Therapeutic Target 24110.5 Concluding Remarks 246References 24711 Ligand Discovery for the Nutrient Transporters ASCT2 and LAT-1 from Homology Modeling and Virtual Screening 253Claire Colas and Avner Schlessinger11.1 Solute Carriers in Cancer Metabolism 25311.2 In Silico Methods for Structure-based Drug Design 25511.3 Emerging Cancer Metabolism Targets 26011.4 Conclusions and Future Outlook 263Acknowledgment 265References 26512 Organic Anion Transporting Polypeptides as Drug Targets 271Eleni Kotsampasakou and Gerhard F. Ecker12.1 Introduction 27112.2 OATPs and Genetic Diseases 28512.3 OATPs and Cancer 28612.4 OATPs as Diagnostic Markers 30112.5 OATPs and Selective Delivery of Drugs 30112.6 Potential Protective Role of OATPs 30912.7 OATPs and Drug–Drug Interactions 31112.8 Conclusions and Outlook 312Acknowledgments 313Abbreviation List 313References 314Index 325

Gerhard Ecker is Full Professor for Pharmacoinformatics at the Department of Pharmaceutical Chemistry, University of Vienna (Austria). His main scientific interests are pharmacoinformatic approaches to target drug transporters, in silico screening methods for promiscuous targets and antitargets, and new approaches for data integration and data mining. Rasmus Pr?torius Clausen is Associate Professor at Dept. Drug Design and Pharmacology, University of Copenhagen (former Royal School of Pharmacy) where he also did post-doctoral studies with P. Krogsgaard-Larsen. His main research topics are neuromedicinal chemistry with focus on glutamate, GABA and GHB, and epigenetic medicinal chemistry. He has a M.Sc. degree from University of Southern Denmark (Chemistry/Cell Biology) and a PhD degree from the University of Aarhus (Denmark). Harald Sitte studied Medicine at the Universities of Innsbruck and Vienna (Austria). He was appointed Professor for Psychopharmacology at Vienna Medical University in 2010. His main scientific research interests are the structure-function relationships in neurotransmitter transporters and the pharmacological activity of psychopharmacological medicines and drugs of abuse.

• Preface XIIIA Personal Foreword XVII1 Insights into Transporter Classifications: an Outline of Transporters as Drug Targets 1Michael Viereck, Anna Gaulton, and Daniela Digles1.1 Introduction 11.2 Available Transporter Classifications 21.3 Function versus Sequence Similarity 71.4 Merged Top-Level Transporter Classification 71.5 Choice and Design of the New ChEMBL Classification 111.6 Transporter as Drug Targets 121.7 Drug Targets in the SLC Classification 151.8 Conclusions 17Acknowledgment 17References 182 New Trends in Antidepressant Drug Research 21Benny Bang-Andersen, Klaus P. Bøgesø, Jan Kehler, and Connie Sánchez2.1 Introduction 212.2 Reuptake Blockers 262.3 Multimodal Drugs 362.4 Conclusions 42List of Abbreviations 42References 433 The Molecular Basis of the Interaction Between Drugs and Neurotransmitter Transporters 53Harald H. Sitte, Thomas Stockner, and Michael Freissmuth3.1 Introduction 533.2 Crystal Structures of SLC6 Transporters 553.3 The Binding Site Proper 603.4 The Transport Cycle 613.5 Conclusions and Perspectives 63Acknowledgments 64References 644 γ-Aminobutyric Acid and Glycine Neurotransmitter Transporters 69Petrine Wellendorph, Julie Jacobsen, Jonas Skovgaard-Petersen, Andreas Jurik, Stine B. Vogensen, Gerhard Ecker, Arne Schousboe, Povl Krogsgaard-Larsen, and Rasmus P. Clausen4.1 Introduction 694.2 GABA Transporters 734.3 Glycine Transporters 904.4 Conclusions and Future Perspectives 95References 965 ABC Transporters: From Targets to Antitargets and Back 107Gerhard F. Ecker5.1 Introduction 1075.2 ABC Transporter as Drug Targets 1095.3 ABC Transporter: from Targets to Antitargets 1115.4 Pharmacochaperones and Beyond 1135.5 Conclusions and Outlook 114Acknowledgment 115References 1156 ABC Transporters Involved in Cholestasis 119Frans J. C. Cuperus, Julien Gautherot, Emina Halilbasic, Thierry Claudel, and Michael Trauner6.1 Introduction 1196.2 Canalicular ABC Transporters 1226.3 Basolateral ABC Transporters 1366.4 Nuclear Receptors as Drug Targets 1406.5 Ursodeoxycholic Acid Treatment in Cholestatic Liver Disease 1446.6 Conclusions 145References 1457 Recent Advances in Structural Modeling of ABC Transporters 167Dennis Haake, Peter Chiba, and Gerhard F. Ecker7.1 Introduction 1677.2 ABC Transporter Modeling Attempts Since 2001 1687.3 Retraction of Five Transporter Structures 1707.4 First Mammalian ABC Transporter Structure 1737.5 Conclusions and Perspectives 175Acknowledgment 175References 1758 PET Imaging of ABC Transporters at the Blood–Brain Barrier 179Oliver Langer8.1 The Blood–Brain Barrier 1798.2 The Brain as a Pharmacological Sanctuary 1808.3 Implication of ABC Transporters in Neurological Disorders 1808.4 Positron Emission Tomography 1818.5 PET Imaging of ABC Transporters 1818.6 Challenges in Designing PET Tracers for ABC Transporters 1848.7 Potential Applications of PET Tracers for ABC Transporters 1848.8 Overview of Available PET Tracers for Cerebral ABC Transporters 1858.9 Summary 191Abbreviations 191References 1919 The Systems Biology of Transporters – Targeting the Regulatory System for Transporters (FXR/RXR) 199Antimo Gioiello, Maura Marinozzi, Bruno Cerra, Chiara Custodi, Roberto Pellicciari, and Antonio Macchiarulo9.1 Introduction 1999.2 Discovery and Pharmacological Characterization of FXR 2009.3 Regulation of the Hepatobiliary Transport System by FXR 2019.4 Genetic and Structural Properties of FXR 2079.5 FXR Ligands 2099.6 Conclusions and Perspectives 221References 22110 ANO1 as a Novel Drug Target 231Anke Bill and Larry Alex Gaither10.1 Introduction 23110.2 ANO1: a Calcium Activated Chloride Channel 23210.3 Pharmacological Targeting of ANO1 23810.4 ANO1 as a Therapeutic Target 24110.5 Concluding Remarks 246References 24711 Ligand Discovery for the Nutrient Transporters ASCT2 and LAT-1 from Homology Modeling and Virtual Screening 253Claire Colas and Avner Schlessinger11.1 Solute Carriers in Cancer Metabolism 25311.2 In Silico Methods for Structure-based Drug Design 25511.3 Emerging Cancer Metabolism Targets 26011.4 Conclusions and Future Outlook 263Acknowledgment 265References 26512 Organic Anion Transporting Polypeptides as Drug Targets 271Eleni Kotsampasakou and Gerhard F. Ecker12.1 Introduction 27112.2 OATPs and Genetic Diseases 28512.3 OATPs and Cancer 28612.4 OATPs as Diagnostic Markers 30112.5 OATPs and Selective Delivery of Drugs 30112.6 Potential Protective Role of OATPs 30912.7 OATPs and Drug–Drug Interactions 31112.8 Conclusions and Outlook 312Acknowledgments 313Abbreviation List 313References 314Index 325