Main description:

Applied Biophysics for Drug Discovery is a guide to new techniques and approaches to identifying and characterizing small molecules in early drug discovery. Biophysical methods are reasserting their utility in drug discovery and through a combination of the rise of fragment-based drug discovery and an increased focus on more nuanced characterisation of small molecule binding, these methods are playing an increasing role in discovery campaigns. This text emphasizes practical considerations for selecting and deploying core biophysical method, including but not limited to ITC, SPR, and both ligand-detected and protein-detected NMR.
Topics covered include: Design considerations in biophysical-based lead screening Thermodynamic characterization of protein-compound interactions Characterizing targets and screening reagents with HDX-MS Microscale thermophoresis methods (MST) Screening with Weak Affinity Chromatography Methods to assess compound residence time 1D-NMR methods for hit identification Protein-based NMR methods for SAR development Industry case studies integrating multiple biophysical methods This text is ideal for academic investigators and industry scientists planning hit characterization campaigns or designing and optimizing screening strategies.

Contents:

List of Contributors 1. Introduction Donald Huddler 2. Thermodynamics in Drug Discovery OBrienMarkova&Holdgate 3. Tailoring Hit Identification and Qualification Methods for Targeting Protein-Protein Interactions Bjorn Walse, Andrew P. Turnbull, Susan M. Boyd 4. HYDROGEN DEUTERIUM EXCHANGE MASS SPECTROMETRY IN DRUG DISCOVERY Thorleif Lavold, Roman Zubarev and Juan Astorga-Wells 5. MICROSCALE THERMOPHORESIS IN DRUG DISCOVERY Tanja Bartoschik, Melanie Maschberger, Alessandra Feoli, Timon Andre, Philipp Baaske, Stefan Duhr and Dennis Breitsprecher 6. SPR Screening Applying the new generation of SPR hardware Kartik Narayan and Steve Carroll 7. Weak Affinity Chromatography (WAC) Sten Ohlson* and Minh-Dao Duong-Thi 8. 1D NMR Methods for Hit Identification Mary J Harner, Guille Metzler, Caroline A Fanslau, Luciano Mueller, William J Metzler 9. Protein-Based NMR Methods Applied to Drug Discovery Alessio Bortoluzzi, Alessio Ciulli 10. Applications of Ligand and Protein-observed NMR in Discovery Isabelle Krimm Conclusion 11. Using Biophysical Methods to Optimize Compound Residence Time G. A. Holdgate, P. Rawlins, M. Bista, C. J. Stubbs 12. Applying biophysical and biochemical methods to the discovery of allosteric modulators of the AAA ATPase p97 Stacie L. Bulfer and Michelle R. Arkin 13. Driving Drug Discovery with Biophysical Information Application to Staphylococcus aureus Dihydrofolate Reductase (DHFR) Parag Sahasrabudhe, Veerabahu Shanmugasundaram, Mark Flanagan, Kris A. Borzilleri, Holly Heaslet, Anil Rane, Alex McColl, Tim Subashi, George Karam, Ron Sarver, Melissa Harris, Boris A. Chrunyk, Chakrapani Subramanyam, Thomas V. Magee, Kelly Fahnoe, Brian Lacey, Henry Putz, J. Richard Miller, Jaehyun Cho, Arthur Palmer III and Jane M. Withka 14. Assembly of fragment screening libraries: Property and diversity analysis Bradley C. Doak, Craig J. Morton, Jamie S. Simpson & Martin J. Scanlon Index