05494nam 2200685Ia 450 991013960060332120230725053521.01-283-27369-197866132736971-118-01643-21-118-01642-41-118-01641-6(CKB)2550000000054260(EBL)697481(OCoLC)768204517(SSID)ssj0000555590(PQKBManifestationID)11363476(PQKBTitleCode)TC0000555590(PQKBWorkID)10519627(PQKB)11461308(MiAaPQ)EBC697481(Au-PeEL)EBL697481(CaPaEBR)ebr10501306(CaONFJC)MIL327369(EXLCZ)99255000000005426020101013d2011 uy 0engur|n|---|||||txtccrSystems biology in drug discovery and development[electronic resource] /edited by Daniel L. Young and Seth MichelsonHoboken, New Jersey Wiley20111 online resource (398 p.)Wiley Series on Technologies for the Pharmaceutical Industry ;v.9Description based upon print version of record.0-470-26123-4 Includes bibliographical references.SYSTEMS BIOLOGY IN DRUG DISCOVERY AND DEVELOPMENT; CONTENTS; PREFACE; CONTRIBUTORS; PART I: INTRODUCTION TO SYSTEMS BIOLOGY IN APPROACH; CHAPTER 1: Introduction to Systems Biology in Drug Discovery and Development; SYSTEMS BIOLOGY IN PHARMACOLOGY; REFERENCES; CHAPTER 2: Methods for In Silico Biology: Model Construction and Analysis; 2.1. INTRODUCTION; 2.2. MODEL BUILDING; 2.3. PARAMETER ESTIMATION; 2.4. MODEL ANALYSIS; 2.5. CONCLUSIONS; REFERENCES; CHAPTER 3: Methods in In Silico Biology: Modeling Feedback Dynamics in Pathways; 3.1. INTRODUCTION; 3.2. STATISTICAL MODELING3.3. MATHEMATICAL MODELING3.4. FEEDBACK AND FEEDFORWARD; 3.5. CONCLUSIONS; REFERENCES; CHAPTER 4: Simulation of Population Variability in Pharmacokinetics; 4.1. INTRODUCTION; 4.2. PBPK MODELING; 4.3. SIMULATION OF PHARMACOKINETIC VARIABILITY; 4.4. CONCLUSIONS AND FUTURE DIRECTIONS; REFERENCES; PART II: APPLICATIONS TO DRUG DISCOVERY; CHAPTER 5: Applications of Systems Biology Approaches to Target Identification and Validation in Drug Discovery; 5.1. INTRODUCTION; 5.2. TYPICAL DRUG DISCOVERY PARADIGM; 5.3. INTEGRATED DRUG DISCOVERY5.4. DRIVERS OF THE DISEASE PHENOTYPE: CLINICAL ENDPOINTS AND HYPOTHESES5.5. EXTRACELLULAR DISEASE DRIVERS: MECHANISTIC BIOTHERAPEUTIC MODELS; 5.6. RELEVANT CELL MODELS FOR CLINICAL ENDPOINTS; 5.7. INTRACELLULAR DISEASE DRIVERS: SIGNALING PATHWAY QUANTIFICATION; 5.8. TARGET SELECTION: DYNAMIC PATHWAY MODELING; 5.9. CONCLUSIONS; REFERENCES; CHAPTER 6: Lead Identification and Optimization; 6.1. INTRODUCTION; 6.2. THE SYSTEMS BIOLOGY TOOL KIT; 6.3. CONCLUSIONS; REFERENCES; CHAPTER 7: Role of Core Biological Motifs in Dose-Response Modeling: An Example with Switchlike Circuits7.1. INTRODUCTION: SYSTEMS PERSPECTIVES IN DRUG DISCOVERY7.2. SYSTEMS BIOLOGY AND TOXICOLOGY; 7.3. MECHANISTIC AND COMPUTATIONAL CONCEPTS IN A MOLECULAR OR CELLULAR CONTEXT; 7.4. RESPONSE MOTIFS IN CELL SIGNALING AND THEIR ROLE IN DOSE RESPONSE; 7.5. DISCUSSION AND CONCLUSIONS; REFERENCES; CHAPTER 8: Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling During Discovery and Early Development; 8.1. INTRODUCTION; 8.2. CHALLENGES IN DRUG DISCOVERY AND DEVELOPMENT; 8.3. METHODOLOGICAL ASPECTS AND CONCEPTS; 8.4. USE OF PK-PD MODELS IN LEAD OPTIMIZATION8.5. USE OF PK-PD MODELS IN CLINICAL CANDIDATE SELECTION8.6. ENTRY-INTO-HUMAN PREPARATION AND TRANSLATIONAL PK-PD MODELING; 8.7. USE OF PK-PD MODELS IN TOXICOLOGY STUDY DESIGN AND EVALUATION; 8.8. JUSTIFICATION OF STARTING DOSE, CALCULATION OF SAFETY MARGINS, AND SUPPORT OF PHASE I DESIGN; 8.9. PHASE I AND BEYOND; 8.10. SUPPORT OF EARLY FORMULATION DEVELOPMENT; 8.11. OUTLOOK AND CONCLUSIONS; REFERENCES; PART III: APPLICATIONS TO DRUG DEVELOPMENT; CHAPTER 9: Developing Oncology Drugs Using Virtual Patients of Vascular Tumor Diseases; 9.1. INTRODUCTION; 9.2. MODELING ANGIOGENESIS9.3. USE OF RIGOROUS MATHEMATICAL ANALYSIS TO GAIN INSIGHT INTO DRUG DEVELOPMENTThe first book to focus on comprehensive systems biology as applied to drug discovery and development Drawing on real-life examples, Systems Biology in Drug Discovery and Development presents practical applications of systems biology to the multiple phases of drug discovery and development. This book explains how the integration of knowledge from multiple sources, and the models that best represent that integration, inform the drug research processes that are most relevant to the pharmaceutical and biotechnology industries. The first book to focus on comprehensive systems biology and its aWiley Series on Technologies for the Pharmaceutical IndustryDrug developmentSystems biologyDrug development.Systems biology.615/.19Young Daniel L969401Michelson Seth534789MiAaPQMiAaPQMiAaPQBOOK9910139600603321Systems biology in drug discovery and development2202855UNINA