Description
Protein and lipid kinases are often the master regulators of cell signaling in eukaryotic systems. The human genome codes for more than 500 of these enzymes and their misregulation has been shown to be involved in the onset and progression of many diseases including cancer and inflammation. Therefore, small molecule kinase inhibitors have become important research tools for the elucidation of the many biological roles of kinases and their mechanisms of action. Kinase inhibitors thus also contribute significantly to the drug pipelines of the pharmaceutical and biotechnology industries and to the growing need to treat cancer and inflammation. In Kinase Inhibitors: Methods and Protocols, experts in kinase biology, drug discovery, and clinical research present a series of exemplary methods that can be used to address the many challenges facing scientists in the discovery and development of kinase inhibitors both for research and clinical use. Written in the highly successful Methods in Molecular Biology(TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Kinase Inhibitors: Methods and Protocols aims to provide scientists with modern and relevant methods to accelerate or strengthen their research and drug discovery programs through the utilization of these vital regulators. 1. Targeting Cancer with Small Molecular Weight Kinase Inhibitors Doriano Fabbro, Sandra W. Cowan-Jacob, Henrik Mbitz, and Georg Martiny-Baron 2. Small Molecule Protein and Lipid Kinase Inhibitors in Inflammation and Specific Models for their Evaluation Matthias Gaestel and Alexey Kotlyarov 3. Measuring the Activity of Leucine Rich Repeat Kinase 2 (LRRK2) – A Kinase Involved in Parkinson’s Disease Byoung Dae Lee, Xiaojie Li, Ted M. Dawson, and Valina L. Dawson 4. Measuring PI3K Lipid Kinase Activity Elisa Ciraolo, Alessia Perino, and Emilio Hirsch 5. A Fluorescence Polarization Assay for the Discovery of Inhibitors of the Polo-box Domain of Polo-like Kinase 1 Wolfgang Reindl, Klaus Strebhardt, and Thorsten Berg 6. Assessment of Hepatotoxicity Potential of Drug Candidate Molecules Including Kinase Inhibitors by Hepatocyte Imaging Assay Technology and Bile Flux Imaging Assay Technology Jinghai J. Xu, Margaret C. Dunn, Arthur R. Smith, and Eric S. Tien 7. Kinase Inhibitor Selectivity Profiling using Differential Scanning Fluorimetry Oleg Fedorov, Frank H. Niesen, and Stefan Knapp 8. Chemoproteomic Characterization of Protein Kinase Inhibitors using Immobilized ATP James S. Duncan, Timothy A.J. Haystead, and David W. Litchfield 9. Proteome-wide identification of staurosporine-binding kinases using Capture Compound Mass Spectrometry Jenny J. Fischer, Olivia Y. Graebner ne Baessler, and Mathias Dreger 10. Affinity Purification of Proteins Binding to Kinase Inhibitors Immobilised on Self Assembling Monolayers Marcus Bantscheff, Scott Hobson, and Bernhard Kuster 11. Kinase Inhibitor Profiling using Chemoproteomics Markus Schirle, Eugene C. Petrella, Scott M. Brittain, David Schwalb, Edmund Harrington, Ivan Cornella-Taracido, and John A. Tallarico 12. Covalent Crosslinking of Kinases with Their Corresponding Peptide Substrates Alexander V. Statsuk and Kevan M. Shokat 13. Receptor Tyrosine Kinase Inhibitor Profiling using Bead-based Multiplex Sandwich Immunoassays Oliver Ptz, Nicole Schneiderhan-Marra, Tanja Henzler, Thomas Herget, and Thomas O. Joos 14. Monitoring Phosphoproteomic Response To Targeted Kinase Inhibitors Using Reverse-Phase Protein Microarrays Gabriela Lavezzari and Mark R. Lackner 15. Measuring Phosphorylation Specific Changes in Response to Kinase Inhibitors in Mammalian Cells Using Quantitative Proteomics Nurhan zl , Marc Kirchner, and Judith Jebanathirajah Steen 16. Investigation of Acquired Resistance to EGFR-Targeted Therapies in Lung Cancer Using cDNA Microarrays Kian Kani, Rafaella Sordella, and Parag Mallick
