LEADER 05494nam 2200685Ia 450 001 9910139600603321 005 20230725053521.0 010 $a1-283-27369-1 010 $a9786613273697 010 $a1-118-01643-2 010 $a1-118-01642-4 010 $a1-118-01641-6 035 $a(CKB)2550000000054260 035 $a(EBL)697481 035 $a(OCoLC)768204517 035 $a(SSID)ssj0000555590 035 $a(PQKBManifestationID)11363476 035 $a(PQKBTitleCode)TC0000555590 035 $a(PQKBWorkID)10519627 035 $a(PQKB)11461308 035 $a(MiAaPQ)EBC697481 035 $a(Au-PeEL)EBL697481 035 $a(CaPaEBR)ebr10501306 035 $a(CaONFJC)MIL327369 035 $a(EXLCZ)992550000000054260 100 $a20101013d2011 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aSystems biology in drug discovery and development$b[electronic resource] /$fedited by Daniel L. Young and Seth Michelson 210 $aHoboken, New Jersey $cWiley$d2011 215 $a1 online resource (398 p.) 225 1 $aWiley Series on Technologies for the Pharmaceutical Industry ;$vv.9 300 $aDescription based upon print version of record. 311 $a0-470-26123-4 320 $aIncludes bibliographical references. 327 $aSYSTEMS 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 MODELING 327 $a3.3. 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 DISCOVERY 327 $a5.4. 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 Circuits 327 $a7.1. 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 OPTIMIZATION 327 $a8.5. 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 ANGIOGENESIS 327 $a9.3. USE OF RIGOROUS MATHEMATICAL ANALYSIS TO GAIN INSIGHT INTO DRUG DEVELOPMENT 330 $aThe first book to focus on comprehensive systems biology as applied to drug discovery and development Drawing on real-life examples, Systems Biology in Drug Discovery and Development presents practical applications of systems biology to the multiple phases of drug discovery and development. This book explains how the integration of knowledge from multiple sources, and the models that best represent that integration, inform the drug research processes that are most relevant to the pharmaceutical and biotechnology industries. The first book to focus on comprehensive systems biology and its a 410 0$aWiley Series on Technologies for the Pharmaceutical Industry 606 $aDrug development 606 $aSystems biology 615 0$aDrug development. 615 0$aSystems biology. 676 $a615/.19 701 $aYoung$b Daniel L$0969401 701 $aMichelson$b Seth$0534789 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910139600603321 996 $aSystems biology in drug discovery and development$92202855 997 $aUNINA