Hit and Lead Profiling
Identification and Optimization of Drug-like Molecules
Methods and Principles in Medicinal Chemistry (Series Nr. 43)
1. Edition August 2009
XXX, 503 Pages, Hardcover
82 Pictures (16 Colored Figures)
35 tables
Handbook/Reference Book
Short Description
By addressing both drug efficiency and drug safety, this modern practical reference shows how each aspect shapes the key decisions for assessing the risk/benefit ratio of any novel compound during the early drug development stages, using both in vitro and in silico methods.
Buy now
Price: 229,00 €
Price incl. VAT, excl. Shipping
Euro prices for Wiley-VCH and Ernst & Sohn titles are only valid for Germany. In EU countries, local VAT applies. Postage will be charged.
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.
1 Process logistics, testing strategies and automation aspects
2 Prediction of drug-likeness and its integration
3 Integrative risk assessment
PART 2: ADME Profiling: What is Drug Likeness?
4 Solubility and Aggregation
5 In silico tools and in vitro HTS approaches to determine lipophilicity during the drug discovery process
6 Membrane permeability - measurement and prediction in drug discovery
7 Drug Metabolism and Reactive Metabolites
8 Drug-Drug Interactions: Screening for liability and assessment of risk
9 Plasma Protein Binding and Volume of Distribution: Determination, Prediction and Use in Early Drug Discovery
10 Putting it all together
PART 3: Safety Profiling: What is Considered Safe in the Clinic?
11 Genetic Toxicity: in vitro Approaches for Hit and Lead Profiling
12 In vitro Safety Pharmacology Profiling: An important tool to decrease attrition
13 Knowledge-based and Computational Approaches to in vitro Safety Pharmacology
PART 4: Organ Specific Toxicity
14 Discovery Toxicology Screening: Predictive, In Vitro Cytotoxicity
15 Predicting Drug-Induced Hepatotoxicity: In Vitro, In Silico, and In Vivo Approaches
16 Should cardiosafety be ruled by hERG inhibition? Early testing scenarios and integrated risk assessment
17 Haematotoxicity: in vitro and ex vivo compound profiling
18 Profiling Adverse Immune Effects
19 In Vitro Phototoxicity Testing: A Procedure Involving Multiple Endpoints
He received his MD and PhD in neurophysiology/neuropharmacology in Hungary, and was visiting professor at Duke University between 1987-1989. He joined the Sandoz Institute for Medical Research, London, in 1990, where he was head of pharmacology. Dr. Urban has published over 130 scientific articles, book chapters and patents and has served on the editorial board of several journals, while also serving as President of the European Neuropeptide Club, between 1999 and 2001.
Bernard Faller is currently director in the Metabolism and Pharmacokinetics department at NIBR, Basel, Switzerland. He graduated as a biochemist from the University of Strasbourg, France, where he obtained his PhD in 1991. He then started at Ciba-Geigy as a post-doctoral fellow, becoming head of laboratory in 1995. In 1999 he moved to central technologies and established the foundations of the Novartis biopharmaceutical profiling group that addresses early ADME properties in drug discovery, and two years later became technology program head for physicochemical profiling in the Preclinical Compound Profiling Unit. In 2007 Dr. Faller was named "Hero of Chemistry" by the ACS for the discovery of Exjade®, the first orally-active iron chelator for the treatment of transfusional iron overload.
