Hit and Lead Profiling

Laszlo Urban is global head of Preclinical Safety Profiling at the Novartis Institutes for Biomedical Research (NIBR), Cambridge, MA, and previously was the Deputy Head of the Novartis Institute for Medical Sciences in London, UK. 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.

PART 1: Introduction: The one Airplane that Flies - Selection of the Right one Molecule for Clinical use.
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

"This book, which is not only for experienced scientists in the pharmaceutical industry, but is suited for newer researchers as well, clearly highlights all the relevant aspects required to facilitate the definition of a compound profile. This is a must-read for those who wish to be introduced to the multifarious aspects of compound profiling with regard to safety and efficacy, which are, in addition to affinity and selectivity, issues that make up the driving force behind a successful drug discovery project." ( ChemMedChem , 2010)