Protein Kinases in Development and Disease discusses and reviews important, but often neglected, kinases. A good representation of current model organisms from plants and C. elegans to mice are used as the basis to illustrate how we can use our understanding of normal development to learn about disease. Reviews kinases, the fundamental regulators of most biological processes that have key roles in the development of all organisms Includes a broad scope of topics that are addressed Allows researchers and newcomers to this research area to gain a thorough picture of the current knowledge
Protein Kinases in Drug Discovery, Volume 124 discusses the latest information on protein kinases and how they modify other proteins by chemically adding phosphate groups to them. New chapters in this release include Transport Proteins and AMPs: Implications in Human Disease, Protein kinase CK2 inhibition as a pharmacological strategy, Emerging role of Protein kinase in diabetes mellitus: From Mechanism to therapy, Dual Roles of ATP-binding site in Protein Kinases: Orthosteric inhibition and Allosteric Regulation, Pseudokinases in drug discovery and development: progress, challenges and future prospects, Comparison of knowledge-based vs. combinatorial peptide library approaches for the identification of protein kinase substrates, and more. Contains timely chapters written by well-renown authorities in their field Includes a number of high-quality illustrations, figures and tables, and targets a very wide audience of specialists, researchers and students Integrates experimental and computational methods for studying the role of protein kinases in different diseases, along with sections on the design of suitable protein kinase inhibitors for use in the treatment of patients
From humble beginnings over 25 years ago as a lipid kinase activity associated with certain oncoproteins, PI3K (phosphoinositide 3-kinase) has been catapulted to the forefront of drug development in cancer, immunity and thrombosis, with the first clinical trials of PI3K pathway inhibitors now in progress. Here we give a brief overview of some key discoveries in the PI3K area and their impact, and include thoughts on the current state of the field, and where it could go from here
Mitogen-activated protein kinases (MAPK) are a large family of enzymes that function as signal transducers to regulate a diverse range of physiological responses. However, signaling via extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK), and p38 MAPK also underpin many disease processes. This Special Issue provides new insights into how MAPK signaling contributes to specific pathological processes across a range of conditions, including disorders of lung development, type 2 diabetes, proliferative skin diseases, cardiovascular diseases, and neurological diseases.
Leading researchers, from the Novartis group that pioneered Gleevec/GlivecTM and around the world, comprehensively survey the state of the art in the drug discovery processes (bio- and chemoinformatics, structural biology, profiling, generation of resistance, etc.) aimed at generating PTK inhibitors for the treatment of various diseases, including cancer. Highlights include a discussion of the rationale and the progress made towards generating "selective" low molecular-weight kinase inhibitors; an analysis of the normal function, role in disease, and application of platelet-derived growth factor antagonists; and a summary of the factors involved in successful structure-based drug design. Additional chapters address the advantages and disadvantages of in vivo preclinical models for testing protein kinase inhibitors with antitumor activity and the utility of different methods in the drug discovery and development process for determining "on-target" vs "off-target" effects of kinase inhibitors.
PI3K has become a very intense area of research, with over 2000 publications on PI3K in PubMed for 2009 alone. The expectations for a therapeutic impact of intervention with PI3K activity are high, and progress in the clinical arena is being monitored by many. However, targeted therapies almost invariably encounter roadblocks, often exposing unresolved questions in the basic understanding of the target
The aims of this volume are to highlight the tremendous pharmacological potential of protein kinase and protein phosphatase inhibitors, to provide a thorough overview of the most remarkable achievements in the field and to illustrate how beneficial these studies can be for the advancement of both basic knowledge on biological regulation and deregulation and for the clinical treatment of a wide spectrum of diseases. This goal is attained by contributions of leader investigators in the field, who address the issue from different angles.
Protein Kinase Inhibitors: From Discovery to Therapeutics offers a foundational, pragmatic overview of protein kinases inhibitors and their potential role in disease modulation and treatment. Here, international experts in the field offer an integrated discussion of kinase inhibitor biology, biomarker discovery, and methods for drug design and development. After a brief overview of kinases and kinase inhibitors, subsequent chapters discuss individual kinases that are representative of the wider kinases and kinase families, including their roles in disease pathogenesis, underlying mechanisms, potential inhibitors and their modes of action for therapeutic modulation. Several potential drugs under different stages of clinical trials are discussed, including their relevance to cancer, diabetes, obesity, cardiovascular, neurological, and auto-immune and inflammatory disease, among other disorders. The book also addresses the challenges and opportunities for future kinase inhibitor development. Provides a thorough overview of kinase inhibitor biology and its role in disease progression and modulation Examines protein kinase inhibitor drugs in various stages of clinical trials and development Offers methods and protocols for protein kinase inhibitor research studies and drug design and development Includes chapter contributions from international leaders in the field
Proteins are the work horses of the cell. As regulators of protein function, protein kinases are involved in the control of cellular functions via intricate signalling pathways, allowing for fine tuning of physiological functions. This book is a collaborative effort, with contribution from experts in their respective fields, reflecting the spirit of collaboration - across disciplines and borders - that exists in modern science. Here, we review the existing literature and, on occasions, provide novel data on the function of protein kinases in various systems. We also discuss the implications of these findings in the context of disease, treatment, and drug development.
