Next Generation Kinase Inhibitors

Protein kinases are fascinating enzymes that maintain the proper function of nearly every task performed by the cells of the human body. By extracting a phosphate from the energy molecule ATP and linking it to another protein, protein kinases alter the structure and ultimate function of other proteins. In this way, protein kinases help monitor the extracellular environment and integrate signaling cues that, for the most part, are beneficial for human health and survival. However, protein kinases are often dysregulated and responsible for the initiation and progression of many types of cancers, inflammatory disorders, and other diseases. Thus, decades of research have revealed much about how protein kinases are regulated and approaches to inhibit these enzymes to treat disease. However, nearly 30 years since the identification of the first clinically beneficial small molecule protein kinase inhibitor, there are only a few examples where these drugs provide sustained and durable patientresponses. The goal of this book is to provide biomedical scientists, graduate, and professional degree students insight into different approaches using small molecules to block specific protein kinase functions that promote disease.

This book provides a brief review of drug development efforts and FDA approved kinase inhibitors This book sets the stage and highlights the importance of kinase signaling pathways in physiological processes This book identifies the genetic mutations that lead to kinase dysregulation and how this promotes the growth and survival of cancer cells The book discusses the emergence of resistance to kinase inhibitors

Autorentext

Paul Shapiro has a long-standing interest in protein kinases and their role in regulating cellular functions during disease. Specific areas focus on the discovery and development of function-selective mitogen-activated protein (MAP) kinase inhibitors with the goal of mitigating cancer cell proliferation and inflammation-induced lung injury associated with respiratory diseases. He received a Bachelor of Science degree from the University of Wisconsin-Madison and his doctorate in molecular physiology and biophysics from the University of Vermont. Dr. Shapiro completed post-doctoral training in the Department of Chemistry and Biochemistry at the University of Colorado-Boulder and is currently a professor of Pharmaceutical Sciences at the University of Maryland School of Pharmacy.

Inhalt

Chapter 1: Introduction to Kinases, Cellular Signaling, and Kinase Inhibitors.- Chapter 2: Overview of Current Type I/II Kinase Inhibitors.- Chapter 3: Avoiding or Co-opting ATP Inhibition: Type III, IV, V, and VI Kinase Inhibitors.- Chapter 4: Structural Features Regulating Kinase Interactions with Regulatory and Substrate Proteins.- Chapter 5: Developing Kinase Inhibitors using Computer-Aided Drug Design Approaches.- Chapter 6: A Toolbox of Structural Biology and Enzyme Kinetics Reveals the Case for ERK Docking Site Inhibition.- Chapter 7: Novel Stabilized Peptide Inhibitors of Protein Kinases.- Chapter 8: Novel peptide-based inhibitors of protein kinases.- Index.