Drug-Like Properties: ... To Toxicity Optimization

Item Information
Item#: 9780128010761
Edition 02
Author Di & Kerns
Cover Hardback
On Hand 0
On Order 0

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, only a fraction have sufficient ADME (absorption, distribution, metabolism, elimination) properties, and acceptable toxicology properties, to become a drug product that will successfully complete human Phase I clinical trials.Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization, Second Edition,provides scientists and students the background and tools to understand, discover, and develop optimal clinical candidates. This valuable resource explores physiochemical properties, including solubility and permeability, before exploring how compounds are absorbed, distributed, and metabolized safely and stably. Review chapters provide context and underscore the importance of key concepts such as pharmacokinetics, toxicity, the blood-brain barrier, diagnosing drug limitations, prodrugs, and formulation. Building on those foundations, this thoroughly updated revision covers a wide variety of current methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties for process and product improvement. From conducting key assays for interpretation and structural analysis, the reader learns to implement modification methods and improve each ADME property.Through valuable case studies, structure-property relationship descriptions, and structure modification strategies,Drug-Like Properties, Second Edition,offers tools and methods for ADME/Tox scientists through all aspects of drug research, discovery, design, development, and optimization.

Provides a comprehensive and valuable working handbook for scientists and students in medicinal chemistryIncludes expanded coverage of pharmacokinetics fundamentals and effectsContains updates throughout, including the authors' recent work in the importance of solubility in drug development; new and currently used property methods, with a reduction of seldom-used methods; and exploration of computational modeling methods

Table of Contents
Chapter 1: IntroductionChapter 2: Benefits of Property Assessment and Good Drug-Like PropertiesChapter 3: In Vivo Environments Affect Drug ExposureChapter 4: Prediction Rules for Rapid Property Profiling from StructureChapter 5: LipophilicityChapter 6: pKaChapter 7: SolubilityChapter 8: PermeabilityChapter 9: TransportersChapter 10: Blood-Brain BarrierChapter 11: Metabolic StabilityChapter 12: Plasma StabilityChapter 13: Solution StabilityChapter 14: Plasma and Tissue BindingChapter 15: Cytochrome P450 InhibitionChapter 16: hERG BlockingChapter 17: ToxicityChapter 18: Integrity and PurityChapter 19: PharmacokineticsChapter 20: Lead PropertiesChapter 21: Strategies for Integrating Drug-Like Properties into Drug DiscoveryChapter 22: Methods for Profiling Drug-Like Properties: General ConceptsChapter 23: Lipophilicity MethodsChapter 24: pKaMethodsChapter 25: Solubility MethodsChapter 26: Permeability MethodsChapter 27: Transporter MethodsChapter 28: Blood-Brain Barrier MethodsChapter 29: Metabolic Stability MethodsChapter 30: Plasma Stability MethodsChapter 31: Solution Stability MethodsChapter 32: CYP Inhibition MethodsChapter 33: Plasma and Tissue Binding MethodsChapter 34: hERG MethodsChapter 35: Toxicity MethodsChapter 36: Integrity and Purity MethodsChapter 37: Pharmacokinetic MethodsChapter 38: Diagnosing and Improving Pharmacokinetic PerformanceChapter 39: ProdrugsChapter 40: Effects of Properties on Biological AssaysChapter 41: Formulation