| Description |
1 online resource |
| Contents |
Intro -- Preface -- Contents -- Contributors -- Introduction to Kinases, Cellular Signaling, and Kinase Inhibitors -- Historical Overview of Protein Kinases and Targeted Inhibition -- Overview of Protein Kinase Signaling Pathways -- Overview of Protein Kinase Structural Features -- References -- Overview of Current Type I/II Kinase Inhibitors -- Introduction -- FDA-Approved Kinase Inhibitors: Type I and II Mechanisms of Action -- Type I Binding Modes -- Type II Binding Modes -- Successes and Limitations -- References |
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Avoiding or Co-Opting ATP Inhibition: Overview of Type III, IV, V, and VI Kinase Inhibitors -- Part A: Type III Kinase Inhibitors -- Part B: Type IV Kinase Inhibitors -- Part C: Type V Kinase Inhibitors -- Part D: Type VI Kinase Inhibitors -- References -- Protein Kinase Interactions with Regulatory and Effector Proteins -- Introduction -- Docking Interactions Between Protein Kinases and Other Proteins -- MAP Kinase Interactions Through the DRS -- MAP Kinase Interactions Through the FRS -- Conclusions -- References -- Developing Kinase Inhibitors Using Computer-Aided Drug Design Approaches |
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Introduction -- Basic Concepts of CADD and Typical CADD Methods -- Applications of CADD Methods for Kinase Inhibitor Development -- Extracellular-Signal-Regulated Kinases (ERK) -- P38 MAP Kinase -- P56 T Cell Tyrosine Kinase (Lck) -- Summary -- References -- A Toolbox of Structural Biology and Enzyme Kinetics Reveals the Case for ERK Docking Site Inhibition -- ERK Overview -- The D-Recruitment Site -- The F-Recruitment Site -- Docking Sites in Catalysis -- The Story of Ets-1 -- Steady-State Kinetics -- Presteady-State Kinetics -- Mutational Studies -- Structural Insights |
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Mechanisms of Docking Site Inhibition -- Reversible Inhibition -- Covalent Inhibition -- Noncatalytic Effects -- Docking Site Inhibitor Development -- Current DRS Inhibitors -- Hydrophobic Groove and CD Domain Inhibitors -- ED Domain Inhibitors -- Current FRS Inhibitors -- The Future of Docking Site Inhibitors -- Summary -- References -- Novel Stabilized Peptide Inhibitors of Protein Kinases -- Introduction -- Targeting Receptor Tyrosine Kinase Dimerization with Stapled Peptides -- Targeting the Extracellular Region of EGFR with Constrained Peptides |
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Targeting the Intracellular Region of EGFR with Stapled Peptides -- RTKs as Peptide Inhibitor Targets -- Disruption of Spatiotemporal Regulation of Kinases with Stapled Peptides -- A Kinase Anchoring Proteins (AKAPs) -- Functional Aspects of AKAP Complexes -- Targeting AKAP Complexes -- Targeting PKA RII Anchoring by AKAPs -- Targeting PKA RI Anchoring by AKAPs -- Targeting AKAP Complexes Beyond PKA Interactions -- Pseudosubstrate Inhibition of Kinases with Stabilized Peptides -- Kinase Pseudosubstrate Interactions -- Protein Kinase Inhibitor (PKI) as a Pseudosubstrate |
| Summary |
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 patient responses. 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 |
| Notes |
Includes index |
| Subject |
Protein kinases -- Inhibitors.
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Oncology.
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Medical -- Oncology.
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Protein kinases -- Inhibitors
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| Genre/Form |
Electronic books
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| Form |
Electronic book
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| Author |
Shapiro, Paul
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| ISBN |
9783030482831 |
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3030482839 |
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