دانلود کتاب Hit and Lead Profiling: Identification and Optimization of Drug-like Molecules, Volume 43

The only reference on current methods to generate pharmacokinetic and safety profiles of drug candidates, as well as how they must be balanced against one other for the best selection of candidates for further development. Following a brief introduction to the necessities of filtering and risk assessment of potential new drug molecules before actual drug development, the two equally important aspects of pharmacological (ADME) and safety (toxicity) profiling are covered in separate parts. The ADME section covers the profiling of basic physicochemical parameters, such as solubility and permeability, as well as more complex traits, such as the likelihood of drug-drug interactions, metabolic clearance and protein binding properties. The toxicology part addresses, among others, recent advances in early genetic toxicity testing, bioactivation screening, organ-specific toxicity assays for liver, heart, kidney and blood, as well as profiling for autoimmune reactions. By addressing both drug efficiency and drug safety, this modern practical reference shows readers how each individual aspect figures in shaping the key decisions on which the entire drug development process hinges. In short, this is a complete toolbox for assessing the risk/benefit ratio for any novel compound during the early drug development stages, using both in vitro and in silico methods. Both editors are based at one of the leading research-driven pharmaceutical companies, and the authors have been recruited from numerous other global players in the field. Invaluable know-how for every medicinal chemist and drug developer.Content: Chapter 1 Process Logistics, Testing Strategies and Automation Aspects (pages 1–24): Hansjoerg Haas, Robert S. DeWitte, Robert Dunn?Dufault and Andreas StelzerChapter 2 Prediction of Drug?Likeness and its Integration into the Drug Discovery Process (pages 25–40): Ansgar Schuffenhauer and Meir GlickChapter 3 Integrative Risk Assessment (pages 41–67): Prof., Dr. Bernard Faller and Dr. Laszlo UrbanChapter 4 Solubility and Aggregation (pages 69–90): William H. StrengChapter 5 In Silico Tools and In Vitro HTS Approaches to Determine Lipophilicity During the Drug Discovery Process (pages 91–116): Sophie Martel, Vincent Gasparik and Pierre?Alain CarruptChapter 6 Membrane Permeability – Measurement and Prediction in Drug Discovery (pages 117–143): Kiyohiko Sugano, Lourdes Cucurull?Sanchez and Joanne BennettChapter 7 Drug Metabolism and Reactive Metabolites (pages 145–163): Alan P. WattChapter 8 Drug–Drug Interactions: Screening for Liability and Assessment of Risk (pages 165–196): Ruth Hyland, R. Scott Obach, Chad Stoner, Michael West, Michael R. Wester, Kuresh Youdim and Michael ZientekChapter 9 Plasma Protein Binding and Volume of Distribution: Determination, Prediction and Use in Early Drug Discovery (pages 197–220): Franco Lombardo, R. Scott Obach and Nigel J. WatersChapter 10 Putting it All Together (pages 221–240): Pamela Berry, Neil Parrott, Micaela Reddy, Pascale David?Pierson and Thierry LaveChapter 11 Genetic Toxicity: In Vitro Approaches for Hit and Lead Profiling (pages 241–271): Richard M Walmsley and Nicholas BillintonChapter 12 In Vitro Safety Pharmacology Profiling: An Important Tool to Decrease Attrition (pages 273–295): Jacques Hamon and Steven WhitebreadChapter 13 Knowledge?Based and Computational Approaches to In Vitro Safety Pharmacology (pages 297–322): Josef Scheiber, Andreas Bender, Kamal Azzaoui and Jeremy JenkinsChapter 14 Discovery Toxicology Screening: Predictive, In Vitro Cytotoxicity (pages 323–343): Peter J. O'BrienChapter 15 Predicting Drug?Induced Hepatotoxicity: In Vitro, In Silico and In Vivo Approaches (pages 345–385): Jinghai J. Xu, Amit S. Kalgutkar, Yvonne Will, James Dykens, Elizabeth Tengstrand and Frank HsiehChapter 16 Should Cardiosafety be Ruled by hERG Inhibition? Early Testing Scenarios and Integrated Risk Assessment (pages 387–413): Dimitri Mikhailov, Martin Traebert, Qiang Lu, Steven Whitebread and William EganChapter 17 Hematotoxicity: In Vitro and Ex Vivo Compound Profiling (pages 415–437): David Brott and Francois PognanChapter 18 Profiling Adverse Immune Effects (pages 439–469): Wim H. De Jong, Raymond Pieters, Kirsten A Baken, Rob J. Vandebriel, Jan?Willem Van Der Laan and Henk Van LoverenChapter 19 In Vitro Phototoxicity Testing: A Procedure Involving Multiple Endpoints (pages 471–494): Laurent Marrot and Jean?Roch Meunier