Description
The major reason for the elevated costs of drug development in the pharmaceutical industry is the high attrition rate. In Target Identification and Validation in Drug Discovery: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to identify and validate new target. These include methods and approaches covering biochemical, cell based, in vivo models and translational methods. Chapters also include selected case reports that demonstrate the integration of these technologies to real life experiences and to demonstrate the multiple use of more than one technology to increase knowledge on a specific target. These Written in the highly successful Methods in Molecular Biology(TM) series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Target Identification and Validation in Drug Discovery: Methods and Protocols contains a comprehensive list of essential methods and clear protocols to follow. Part I- Background 1. The Path to Oncology Drug Target Validation – an Industry Perspective Marta Corts-Cros, Tobias Schmelzle, Volker M. Stucke and Francesco Hofmann Part II- DNA as a tool to Modulate Drug Targets 2. Identification of Aptamers as Specific Binders and Modulators of Cell-Surface Receptor Activity Henning Ulrich and Carsten Wrenger 3. The Design and Structure-functional Properties of DNA-based Immunomodulatory Sequences Nikolai V. Kuznetsov Part III-RNA Interference : From Design to Data Analysis 4. siRNA Design Principles and Off-target Effects Sebastian Petri and Gunter Meister 5. Western Blot Evaluation of siRNA Delivery by pH Responsive Peptides Wanling Liang, A. James Mason and Jenny K.W. Lam 6. High Throughput RNAi Screening for the Identification of Novel Targets Meredith C. Henderson and David O. Azorsa 7. Integration of RNAi and Small Molecule Screens to Identify Targets for Drug Development Konstantinos Drosopoulos and Spiros Linardopoulos 8. CellProfiler and KNIME: Open Source Tools for High Content Screening Martin Stter, Antje Niederlein, Rico Barsacchi, Felix Meyenhofer, Holger Brandl and Marc Bickle 9. PARP Inhibition as a Prototype for Synthetic Lethal Screens Xuesong Liu Part IV-Protein Focused Technologies 10. Structure-Based Target Druggability Assessment Jean-Yves Trosset and Nicolas Vodovar 11. Validating Pharmacological Disruption of Protein-protein Interactions by Acceptor Photobleaching FRET Imaging Janos Roszik, Gbor Tth, Jnos Szllosi and Gyrgy Vereb 12. Systematic Analysis of Complex Signal Transduction Pathways using Protein Fragment Complementation Assays Thomas I. Koblizek, Ann Siehoff and Anthony Pitt 13. Reverse-Phase Protein Microarrays and Their Utility in Drug Development Maria Isabella Sereni , Mariaelena Pierobon,Roberto Angioli Emanuel F. Petricoin III, and Mitchell J. Frederick Part V. Innovative Cell Culture Techniques to Mimic Tissue Microenvironments 14. A Cell Culture System that Mimics Chronic Lymphocytic Leukemia Cells Microenvironment for Drug Screening and Characterization Alessandro Natoni 15. 2-Dimensional vs. 3-Dimensional in vitro Tumor Migration and Invasion Assays Miriam Zimmermann, Carol Box and Suzanne A. Eccles 16. Tumor Spheroid-based Migration Assays for Evaluation of Therapeutic Agents Maria Vinci, Carol Box, Miriam Zimmermann and Suzanne A. Eccles 17. The NeuroSphere Assay (NSA) Applied to Neural Stem Cells (NSCs) and Cancer Stem Cells (CSCs) Rossella Galli Part VI- Genetically Engineered Animal Models to study Gene Functions 18. Genetically Engineered Animal Models for in vivo Target Identification and Validation in Oncology Gemma Texid 19. Target Validation in Mice by Constitutive and Conditional RNAi Aljoscha Kleinhammer, Wolfgang Wurst, Ralf Khn 20. In vivo Target Validation by Inducible RNAi in Human Xenograft Mouse Models Marco Mazzoletti and Gemma Texido Part VII- Translational Methods to validate Biomarkers 21. Brightfield In Situ Hybridization Methods to Discover Gene Amplifications and Rearrangements in Clinical Samples Hiroaki Nitta and Thomas M. Grogan 22. Combined microRNA In Situ Hybridization and Immunohistochemical Detection of Protein Markers Boye Schnack Nielsen and Kim Holmstrm Thomas I. Koblizek, Ann Siehoff and Anthony Pitt
