BACE : lead target for orchestrated therapy of Alzheimer's disease / edited by Varghese John.

Format:

Book

Contributor:

John, Varghese, 1958-

Language:

English

Subjects (All):

Alzheimer's disease--Chemotherapy.

Alzheimer's disease.

Aspartic proteinases--Inhibitors--Therapeutic use.

Aspartic proteinases.

Amyloid beta-protein precursor.

Physical Description:

1 online resource (284 p.)

Edition:

1st ed.

Place of Publication:

Hoboken, NJ : John Wiley & Sons, c2010.

Language Note:

English

Summary:

BACE inhibitors and their use in the treatment of Alzheimer's Disease BACE (ß-site of APP cleaving enzyme) is a critical component in Alzheimer's Disease (AD), and the development of BACE inhibitors shows great potential as a therapy for the disease. BACE: Lead Target for Orchestrated Therapy of Alzheimer's Disease covers virtually all aspects of BACE from initial identification, discovery of inhibitors, and challenges in clinical development, while providing a global understanding essential for productive and successful drug discovery. This book details the story of the disc

Contents:

BACE; CONTENTS; PREFACE; ACKNOWLEDGMENTS; CONTRIBUTORS; CHAPTER 1 BACE, APP PROCESSING, AND SIGNAL TRANSDUCTION IN ALZHEIMER'S DISEASE; 1.1 Introduction; 1.2 BACE Cleavage of APP as a Molecular Switching Mechanism; 1.3 AD: An Imbalance in Cellular Dependence?; 1.4 BACE Cleavage, Caspase Cleavage, and Neuronal Trophic Dependence; 1.5 BACE Cleavage of APP, Dependence Receptors, and Alzheimer Pathology; 1.6 Key Mutations Proximal of APP Processing to Aβ; 1.7 Final Remarks; CHAPTER 2 IDENTIFICATION OF BACE AS A TARGET IN ALZHEIMER'S DISEASE; 2.1 Introduction; 2.2 The Search for β-Secretase

2.3 Validation of the BACE Target 2.4 Final Remarks; CHAPTER 3 BACE BIOLOGICAL ASSAYS; 3.1 Introduction; 3.2 Clinical and Physiological Hallmarks of Alzheimer's Disease (AD); 3.3 APP Processing; 3.4 Aspartyl Protease Classification; 3.5 BACE Structure; 3.6 Mechanism, Kinetics, Inhibition, and Specificity; 3.7 Assay Strategies for Inhibitor Finding and Development; 3.8 Common Assays Used to Identify and Study Inhibitors; 3.9 BACE Assays; 3.10 Final Remarks; CHAPTER 4 PEPTIDIC, PEPTIDOMIMETIC, AND HTS-DERIVED BACE INHIBITORS; 4.1 Introduction; 4.2 Elan/Pharmacia (Pfizer)

4.3 Oklahoma Medical Research Foundation (OMRF)/Multiple Collaborators 4.4 Eli Lilly; 4.5 Merck; 4.6 GlaxoSmithKline; 4.7 Schering Plough; 4.8 Bristol-Myers Squibb; 4.9 Novartis; 4.10 Amgen; 4.11 Wyeth; 4.12 Final Remarks; CHAPTER 5 FRAGMENT-BASED APPROACHES FOR IDENTIFICATION OF BACE INHIBITORS; 5.1 Introduction; 5.2 Biophysical Methods Applied to BACE Fragment Screens; 5.3 BACE Inhibitors Identified by Fragment Screening; 5.4 Final Remarks; CHAPTER 6 STRUCTURE-BASED DESIGN OF BACE INHIBITORS: TECHNICAL AND PRACTICAL ASPECTS OF PREPARATION, 3-DIMENSIONAL STRUCTURE, AND COMPUTATIONAL ANALYSIS

6.1 Introduction 6.2 Preparation of BACE for Structural Studies; 6.3 Crystallographic Studies of BACE; 6.4 Structural Studies with BACE Inhibitors: Peptidomimetics and Nonpeptidomimetics; 6.5 Computational Approaches; 6.6 Final Remarks; CHAPTER 7 PHARMACOLOGICAL MODELS FOR PRECLINICAL TESTING: FROM MOUSE TO DOG TO NONHUMAN PRIMATES; 7.1 Introduction; 7.2 BACE 1 and Mouse Models of AD; 7.3 Testing BACE Inhibitors in the Canine Model of Human Aging and AD; 7.4 BACE Inhibitors and Nonhuman Primates; 7.5 Final Remarks

CHAPTER 8 ADSORPTION, DISTRIBUTION, METABOLISM, EXCRETION (ADME), EFFICACY, AND TOXICOLOGY FOR BACE INHIBITORS 8.1 Introduction; 8.2 Development of BACE Inhibitors with Optimized ADME Properties; 8.3 In Vivo Efficacy of BACE Inhibitors; 8.4 Toxicology of BACE Inhibitors; 8.5 Final Remarks; CHAPTER 9 CLINICAL TRIALS FOR DISEASE-MODIFYING DRUGS SUCH AS BACE INHIBITORS; 9.1 Introduction; 9.2 Update on Beta-Amyloid Therapies in Clinical Development; 9.3 Clinical Development of BACE Inhibitors and Other Disease-Modifying Drugs; 9.4 Final Remarks

CHAPTER 10 FUTURE STRATEGIES FOR DEVELOPMENT OF NOVEL BACE INHIBITORS: ANTI-APP β-SITE ANTIBODY AND APP BINDING SMALL MOLECULE APPROACHES FOR ALZHEIMER'S DISEASE

Notes:

Description based upon print version of record.

Includes bibliographical references and index.

Description based on metadata supplied by the publisher and other sources.

ISBN:

9786612491757

9781282491755

128249175X

9780470594087

047059408X

9780470594070

0470594071

OCLC:

612346151