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This practical reference for medicinal and pharmaceutical chemists combines the theoretical background with modern methods as well as applications from recent lead finding and optimization projects.
Divided into two parts on the thermodynamics and kinetics of drug-receptor interaction, the text provides the conceptual and methodological basis for characterizing binding mechanisms for drugs and other bioactive molecules. It covers all currently used methods, from experimental approaches, such as ITC or SPR, right up to the latest computational methods. Case studies of real-life lead or drug development projects are also included so readers can apply the methods learned to their own projects. Finally, the benefits of a thorough binding mode analysis for any drug development project are summarized in an outlook chapter written by the editors.
List of contents
SECTION I: THERMODYNAMICS
The Binding Thermodynamics of Drug Candidates
Van't Hoff-based Thermodynamics
Computation of Drug Binding Thermodynamics
Thermodynamics Guided Optimizations in Medicinal Chemistry
From Molecular Understanding to Structure-Thermodynamic Relationships: the Case of Acetylcholine Binding Proteins
Thermodynamics in Lead Optimisation
Lead Optimization Case Study: Thermodynamic Profiling of Carbonic Anhydrase Inhibitors
SECTION II: KINETICS
Drug-Target Residence Time
Experimental Methods to Determine Binding Kinetics
Challenges in the Medicinal Chemical Optimisation of Binding Kinetics
Computational Approaches for Studying Drug Binding Kinetics
The Use of Structural Information to Understand Binding Kinetics
Importance of Drug-Target Residence Time at G Protein-coupled Receptors - a Case for the Adenosine Receptors
Case Study: Angiotensin Receptor Blockers (ARBs)
The Kinetics and Thermodynamics of Staphylococcus aureus FabI Inhibition
SECTION III: PERSPECTIVE
Thermodynamics and Binding Kinetics in Drug Discovery
About the author
Hugo Kubinyi gehört seit 1985 der BASF AG an, wo Kombinatorische Chemie, Molecular Modelling und Wirkstoffdesign zu seinen Tätigkeitsfeldern zählten. Sein Spezialgebiet sind Struktur-Wirkungs-Beziehungen und QSAR-Methoden.
Gerd Folkers is professor of pharmaceutical chemistry at the ETH Zürich since 1991. He studied pharmacy at the University of Bonn and earned his Ph.D. on structure-activity relationships of desapurines. He then moved to the University of Tübingen, where he completed his habilitation in pharmaceutical chemistry. During a stay with H.-D. Hoeltje in Bern, he studied new research methods in computer-aided molecular design and expanded this knowledge during other stays with T. Blundell at the Birkbeck College and E. Meyer at Texas A&M University.The focus of his research is the molecular interaction between drugs and their binding sites. Besides his work on the molecular mechanism of "conventional" nucleoside therapeutics against virus infections and cancer, his special interest has shifted to immuno-therapeutics.
Summary
This practical reference for medicinal and pharmaceutical chemists combines the theoretical background with modern methods as well as applications from recent lead finding and optimization projects.
Divided into two parts on the thermodynamics and kinetics of drug-receptor interaction, the text provides the conceptual and methodological basis for characterizing binding mechanisms for drugs and other bioactive molecules. It covers all currently used methods, from experimental approaches, such as ITC or SPR, right up to the latest computational methods. Case studies of real-life lead or drug development projects are also included so readers can apply the methods learned to their own projects. Finally, the benefits of a thorough binding mode analysis for any drug development project are summarized in an outlook chapter written by the editors.
