SHAYNE COX GAD, PhD, DABT, ATS, is the Principal of Gad Consulting Services. He has more than thirty years of experience as a toxicologist, statistical consultant, manager, and consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He is the author of forty-two books and numerous papers, presentations, and other publications.

“The text is well-written and includes extensive references.”  (Book News, 1 April 2012)

• PREFACE ix CONTRIBUTORS xiPART I FUNDAMENTAL CONCEPTS 11. Current Needs for New Therapeutic Agents and Discovery Strategies—A Systems Pharmacology Approach 3Sophie C. Desbiens and David H. Farb2. Target Selection in Drug Discovery 25Charles F. Albright3. New Drug Applications 35John S. McInnes and Donald O. Beers4. From Concept to the Clinics: Development of Cancer Therapeutics 47Balveen Kaur, Gregory B. Lesinski, and Abhik Ray Chaudhary5. Development of Countermeasures for Bioterrorism in the United States 73Gregory H. Levine and Jeffrey I. Handwerker6. Development and Application of Conformation-Selective Integrin Antibodies 91Nathan S. Astrof, Dan Peer, and Motomu Shimaoka7. Pain Management Market Overview 113Anita Holdcroft8. Antiviral Market Overview 127Anita Arora, Natalia Mendoza, and Stephen K. TyringPART II METHODS AND TECHNIQUES IN DRUG DISCOVERY AND DEVELOPMENT 1459. High-Throughput Screening for Small-Molecule Drug Discovery 147C. Parker and J.-H. Zhang10. Mass Spectrometry 181Robert D. English and Anthony M. Haag11. Molecular Screening for Therapeutic Agents 207R. Damoiseaux12. Accelerator Mass Spectrometry and Positron Emission Tomography in Human Microdosing 241Zhengdong Cheng13. Development of Antimicrobial Peptides as Therapeutic Agents 285Robert S. Hodges, Ziqing Jiang, James Whitehurst, and Colin T. Mant14. Antibodies for Human Diseases 359Guo-Liang Yu and Jian Ni15. Combinatorial Compounds and Drug Discovery 399James C. Bigelow16. Locoregional Chemoradiotherapy of Cancer Using Hydrogel 413David J. Yang, Ali Azhdarinia, Hiroaki Kurihara, and E. Edmund Kim17. RNAi-Mediated Therapeutics 425Nuria Morral and Scott R. Witting18. Crystallography 445Carl H. Schwalbe19. PEGylation 463Sanju Dhawan, Deepak N. Kapoor, Rishi Kapil, Mano Kumarj, and Ankur Bansal20. Gold Standard Animal Models 517Carol Casteneda and Michael S. LaPointe21. Discovery of Vaccine Adjuvants 533Fiona A. Sharp and Ed C. Lavelle22. Oral Delivery of Macromolecules for the Development of Therapeutic Agents 547Hye J. Lee and Chanmi Choi23. Aerosol Drug Delivery to the Lungs 565Andrew R. Martin and Warren H. Finlay24. Resistance to Antiplatelet Theraphy 589Paul A. Gurbel, Udaya S. Tantry, and Mark J. Antonino25. Antibiotic Development 611Robert L. Bettiker and Jason C. GallagherPART III THERAPEUTIC TOPICS 62926. Antimicrobial Resistance in Biofi lms: A Sticky Situation 631Shu Yeong Queck and Michael Otto27. Drotrecogin Alfa Activated (Recombinant Human Activated Protein C, Xigris) 645Byungse Suh and Rafi k Samuel28. Anti-Inflammatory Therapeutics 655Marion M. Chan and Dunne Fong29. Anti-Inflammatory/Analgesics: An In-depth Look at p38 MAP Kinases 673Kelly L. Brown30. Cardiovascular Disease: In-Depth Look 707Nicholas B. Norgard and Mazen Abu-Fadel31. Ezetimibe and Cholesterol Absorption 723Stefan Oswald and Werner Siegmund32. Cardiology—In-Depth Look: Kinases as Therapeutic Targets in the Heart 743Karin Mauer and J. Emilio Exaire33. Statins in the Reduction of Cardiovascular Events 773Rajesh Sachdeva, Bradley Hughes, and Jawahar L. Mehta34. Cardiology—In-Depth Look: Advances in Antiplatelet Theraphy 785Karin Mauer and Jorge F. Saucedo35. Gastrointestinal Disorders: A Focus on Acid-Suppressive Agents 813Brian Hemstreet36. Pharmacology of Vasopressin and the Renin—Angiotension—Aldosterone System 825Elizabeth J. Brant and Julian L. Seifter37. New Drugs and Nutaceutical in the Treatment of Osteoarthristis 847Y. Henrotin and J. Y. Reginster38. Development of Anticytokine Agents for Rheumatoid Arthritis 881Jonathan Sherlock, Christopher D. Buckley, and Karim Raza39. Overview of CNS Neuropharmaceuticals 897Tauser Roxana-Georgiana and Antohe Dan-Stefan40. Thinking Outside the Box in Alzheimer Disease Treatment 929Rudy J. Castellani, Michael W. Marlatt, Akihiko Nunomura, Paula I. Moreira, Hyoung-Gon Lee, Gemma Casadesus, Xiogwei Zhu, George Perry, and Mark A, Smith41. Neurotrophic Factors as Novel Therapeutic Targets 943Stephen D. Skaper42. Oncology 963Arkadiusz Z. Dudek and Steven F. Powell43. Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia 999Muhammad Mansoor Alam and Moshe Talpaz44. Aromatase Inhibitors for Breast Cancer 1011Akm Hossain and Jame Abraham45. Evolution of Selective Estrogen and Androgen Receptor Modulators: Status of Current Therapy and New Drug Development 1019Gregory T. Wurz and Michael W. DeGregorio46. In-Depth Look: anti-TNF-α Therapies 1045Satadal Chatterjee and Shobhan Gaddameedhi47. Development of Therapeutic Agents: The Maternal—Fetal Perspective 1093C. Gedeon, F. Garcia Bournissen and G. Koren48. History of Antipsychotic Drug Development 1111Shankar S. Gollapudi and Rajan Radhakrishnan49. Radiopharmaceuticals and Medical Imaging: Development of Radioimmumoconjugates for Radioimmunoimaging and Radioimmunotherapy of Malignant Diseases 1137Gang Niu and Xiaoyuan Chen50. Therapeutic Drug Development for Kidney Diseases 1159Mitchell H. Rosner, Joshua King, and Peter Monteleone51. Targeting Chemokines and Angiogenesis in Arthritis 1185Zoltan Szekaneez and Alisa E Koch52. Development of Therapeutic Agents: Methods and Approaches in the Development of Vaccines against Protozoan Parasites 1207Catherine Ivory and Kris Chadee53. Toxicology 1221John H. Duffus54. The Development of Phosphodiesterase 4 Inhibitors for Allergic and Nonallergic Infl ammatory Diseases of the Airways 1233Mark A. GiembyczINDEX 1251

SHAYNE COX GAD, PhD, DABT, ATS, is the Principal of Gad Consulting Services. He has more than thirty years of experience as a toxicologist, statistical consultant, manager, and consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He is the author of forty-two books and numerous papers, presentations, and other publications.

“The text is well-written and includes extensive references.”  (Book News, 1 April 2012)

• PREFACE ix CONTRIBUTORS xiPART I FUNDAMENTAL CONCEPTS 11. Current Needs for New Therapeutic Agents and Discovery Strategies—A Systems Pharmacology Approach 3Sophie C. Desbiens and David H. Farb2. Target Selection in Drug Discovery 25Charles F. Albright3. New Drug Applications 35John S. McInnes and Donald O. Beers4. From Concept to the Clinics: Development of Cancer Therapeutics 47Balveen Kaur, Gregory B. Lesinski, and Abhik Ray Chaudhary5. Development of Countermeasures for Bioterrorism in the United States 73Gregory H. Levine and Jeffrey I. Handwerker6. Development and Application of Conformation-Selective Integrin Antibodies 91Nathan S. Astrof, Dan Peer, and Motomu Shimaoka7. Pain Management Market Overview 113Anita Holdcroft8. Antiviral Market Overview 127Anita Arora, Natalia Mendoza, and Stephen K. TyringPART II METHODS AND TECHNIQUES IN DRUG DISCOVERY AND DEVELOPMENT 1459. High-Throughput Screening for Small-Molecule Drug Discovery 147C. Parker and J.-H. Zhang10. Mass Spectrometry 181Robert D. English and Anthony M. Haag11. Molecular Screening for Therapeutic Agents 207R. Damoiseaux12. Accelerator Mass Spectrometry and Positron Emission Tomography in Human Microdosing 241Zhengdong Cheng13. Development of Antimicrobial Peptides as Therapeutic Agents 285Robert S. Hodges, Ziqing Jiang, James Whitehurst, and Colin T. Mant14. Antibodies for Human Diseases 359Guo-Liang Yu and Jian Ni15. Combinatorial Compounds and Drug Discovery 399James C. Bigelow16. Locoregional Chemoradiotherapy of Cancer Using Hydrogel 413David J. Yang, Ali Azhdarinia, Hiroaki Kurihara, and E. Edmund Kim17. RNAi-Mediated Therapeutics 425Nuria Morral and Scott R. Witting18. Crystallography 445Carl H. Schwalbe19. PEGylation 463Sanju Dhawan, Deepak N. Kapoor, Rishi Kapil, Mano Kumarj, and Ankur Bansal20. Gold Standard Animal Models 517Carol Casteneda and Michael S. LaPointe21. Discovery of Vaccine Adjuvants 533Fiona A. Sharp and Ed C. Lavelle22. Oral Delivery of Macromolecules for the Development of Therapeutic Agents 547Hye J. Lee and Chanmi Choi23. Aerosol Drug Delivery to the Lungs 565Andrew R. Martin and Warren H. Finlay24. Resistance to Antiplatelet Theraphy 589Paul A. Gurbel, Udaya S. Tantry, and Mark J. Antonino25. Antibiotic Development 611Robert L. Bettiker and Jason C. GallagherPART III THERAPEUTIC TOPICS 62926. Antimicrobial Resistance in Biofi lms: A Sticky Situation 631Shu Yeong Queck and Michael Otto27. Drotrecogin Alfa Activated (Recombinant Human Activated Protein C, Xigris) 645Byungse Suh and Rafi k Samuel28. Anti-Inflammatory Therapeutics 655Marion M. Chan and Dunne Fong29. Anti-Inflammatory/Analgesics: An In-depth Look at p38 MAP Kinases 673Kelly L. Brown30. Cardiovascular Disease: In-Depth Look 707Nicholas B. Norgard and Mazen Abu-Fadel31. Ezetimibe and Cholesterol Absorption 723Stefan Oswald and Werner Siegmund32. Cardiology—In-Depth Look: Kinases as Therapeutic Targets in the Heart 743Karin Mauer and J. Emilio Exaire33. Statins in the Reduction of Cardiovascular Events 773Rajesh Sachdeva, Bradley Hughes, and Jawahar L. Mehta34. Cardiology—In-Depth Look: Advances in Antiplatelet Theraphy 785Karin Mauer and Jorge F. Saucedo35. Gastrointestinal Disorders: A Focus on Acid-Suppressive Agents 813Brian Hemstreet36. Pharmacology of Vasopressin and the Renin—Angiotension—Aldosterone System 825Elizabeth J. Brant and Julian L. Seifter37. New Drugs and Nutaceutical in the Treatment of Osteoarthristis 847Y. Henrotin and J. Y. Reginster38. Development of Anticytokine Agents for Rheumatoid Arthritis 881Jonathan Sherlock, Christopher D. Buckley, and Karim Raza39. Overview of CNS Neuropharmaceuticals 897Tauser Roxana-Georgiana and Antohe Dan-Stefan40. Thinking Outside the Box in Alzheimer Disease Treatment 929Rudy J. Castellani, Michael W. Marlatt, Akihiko Nunomura, Paula I. Moreira, Hyoung-Gon Lee, Gemma Casadesus, Xiogwei Zhu, George Perry, and Mark A, Smith41. Neurotrophic Factors as Novel Therapeutic Targets 943Stephen D. Skaper42. Oncology 963Arkadiusz Z. Dudek and Steven F. Powell43. Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia 999Muhammad Mansoor Alam and Moshe Talpaz44. Aromatase Inhibitors for Breast Cancer 1011Akm Hossain and Jame Abraham45. Evolution of Selective Estrogen and Androgen Receptor Modulators: Status of Current Therapy and New Drug Development 1019Gregory T. Wurz and Michael W. DeGregorio46. In-Depth Look: anti-TNF-α Therapies 1045Satadal Chatterjee and Shobhan Gaddameedhi47. Development of Therapeutic Agents: The Maternal—Fetal Perspective 1093C. Gedeon, F. Garcia Bournissen and G. Koren48. History of Antipsychotic Drug Development 1111Shankar S. Gollapudi and Rajan Radhakrishnan49. Radiopharmaceuticals and Medical Imaging: Development of Radioimmumoconjugates for Radioimmunoimaging and Radioimmunotherapy of Malignant Diseases 1137Gang Niu and Xiaoyuan Chen50. Therapeutic Drug Development for Kidney Diseases 1159Mitchell H. Rosner, Joshua King, and Peter Monteleone51. Targeting Chemokines and Angiogenesis in Arthritis 1185Zoltan Szekaneez and Alisa E Koch52. Development of Therapeutic Agents: Methods and Approaches in the Development of Vaccines against Protozoan Parasites 1207Catherine Ivory and Kris Chadee53. Toxicology 1221John H. Duffus54. The Development of Phosphodiesterase 4 Inhibitors for Allergic and Nonallergic Infl ammatory Diseases of the Airways 1233Mark A. GiembyczINDEX 1251

SHAYNE COX GAD, PhD, DABT, ATS, is the Principal of Gad Consulting Services. He has more than thirty years of experience as a toxicologist, statistical consultant, manager, and consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He is the author of forty-two books and numerous papers, presentations, and other publications.

“The text is well-written and includes extensive references.”  (Book News, 1 April 2012)

• PREFACE ix CONTRIBUTORS xiPART I FUNDAMENTAL CONCEPTS 11. Current Needs for New Therapeutic Agents and Discovery Strategies—A Systems Pharmacology Approach 3Sophie C. Desbiens and David H. Farb2. Target Selection in Drug Discovery 25Charles F. Albright3. New Drug Applications 35John S. McInnes and Donald O. Beers4. From Concept to the Clinics: Development of Cancer Therapeutics 47Balveen Kaur, Gregory B. Lesinski, and Abhik Ray Chaudhary5. Development of Countermeasures for Bioterrorism in the United States 73Gregory H. Levine and Jeffrey I. Handwerker6. Development and Application of Conformation-Selective Integrin Antibodies 91Nathan S. Astrof, Dan Peer, and Motomu Shimaoka7. Pain Management Market Overview 113Anita Holdcroft8. Antiviral Market Overview 127Anita Arora, Natalia Mendoza, and Stephen K. TyringPART II METHODS AND TECHNIQUES IN DRUG DISCOVERY AND DEVELOPMENT 1459. High-Throughput Screening for Small-Molecule Drug Discovery 147C. Parker and J.-H. Zhang10. Mass Spectrometry 181Robert D. English and Anthony M. Haag11. Molecular Screening for Therapeutic Agents 207R. Damoiseaux12. Accelerator Mass Spectrometry and Positron Emission Tomography in Human Microdosing 241Zhengdong Cheng13. Development of Antimicrobial Peptides as Therapeutic Agents 285Robert S. Hodges, Ziqing Jiang, James Whitehurst, and Colin T. Mant14. Antibodies for Human Diseases 359Guo-Liang Yu and Jian Ni15. Combinatorial Compounds and Drug Discovery 399James C. Bigelow16. Locoregional Chemoradiotherapy of Cancer Using Hydrogel 413David J. Yang, Ali Azhdarinia, Hiroaki Kurihara, and E. Edmund Kim17. RNAi-Mediated Therapeutics 425Nuria Morral and Scott R. Witting18. Crystallography 445Carl H. Schwalbe19. PEGylation 463Sanju Dhawan, Deepak N. Kapoor, Rishi Kapil, Mano Kumarj, and Ankur Bansal20. Gold Standard Animal Models 517Carol Casteneda and Michael S. LaPointe21. Discovery of Vaccine Adjuvants 533Fiona A. Sharp and Ed C. Lavelle22. Oral Delivery of Macromolecules for the Development of Therapeutic Agents 547Hye J. Lee and Chanmi Choi23. Aerosol Drug Delivery to the Lungs 565Andrew R. Martin and Warren H. Finlay24. Resistance to Antiplatelet Theraphy 589Paul A. Gurbel, Udaya S. Tantry, and Mark J. Antonino25. Antibiotic Development 611Robert L. Bettiker and Jason C. GallagherPART III THERAPEUTIC TOPICS 62926. Antimicrobial Resistance in Biofi lms: A Sticky Situation 631Shu Yeong Queck and Michael Otto27. Drotrecogin Alfa Activated (Recombinant Human Activated Protein C, Xigris) 645Byungse Suh and Rafi k Samuel28. Anti-Inflammatory Therapeutics 655Marion M. Chan and Dunne Fong29. Anti-Inflammatory/Analgesics: An In-depth Look at p38 MAP Kinases 673Kelly L. Brown30. Cardiovascular Disease: In-Depth Look 707Nicholas B. Norgard and Mazen Abu-Fadel31. Ezetimibe and Cholesterol Absorption 723Stefan Oswald and Werner Siegmund32. Cardiology—In-Depth Look: Kinases as Therapeutic Targets in the Heart 743Karin Mauer and J. Emilio Exaire33. Statins in the Reduction of Cardiovascular Events 773Rajesh Sachdeva, Bradley Hughes, and Jawahar L. Mehta34. Cardiology—In-Depth Look: Advances in Antiplatelet Theraphy 785Karin Mauer and Jorge F. Saucedo35. Gastrointestinal Disorders: A Focus on Acid-Suppressive Agents 813Brian Hemstreet36. Pharmacology of Vasopressin and the Renin—Angiotension—Aldosterone System 825Elizabeth J. Brant and Julian L. Seifter37. New Drugs and Nutaceutical in the Treatment of Osteoarthristis 847Y. Henrotin and J. Y. Reginster38. Development of Anticytokine Agents for Rheumatoid Arthritis 881Jonathan Sherlock, Christopher D. Buckley, and Karim Raza39. Overview of CNS Neuropharmaceuticals 897Tauser Roxana-Georgiana and Antohe Dan-Stefan40. Thinking Outside the Box in Alzheimer Disease Treatment 929Rudy J. Castellani, Michael W. Marlatt, Akihiko Nunomura, Paula I. Moreira, Hyoung-Gon Lee, Gemma Casadesus, Xiogwei Zhu, George Perry, and Mark A, Smith41. Neurotrophic Factors as Novel Therapeutic Targets 943Stephen D. Skaper42. Oncology 963Arkadiusz Z. Dudek and Steven F. Powell43. Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia 999Muhammad Mansoor Alam and Moshe Talpaz44. Aromatase Inhibitors for Breast Cancer 1011Akm Hossain and Jame Abraham45. Evolution of Selective Estrogen and Androgen Receptor Modulators: Status of Current Therapy and New Drug Development 1019Gregory T. Wurz and Michael W. DeGregorio46. In-Depth Look: anti-TNF-α Therapies 1045Satadal Chatterjee and Shobhan Gaddameedhi47. Development of Therapeutic Agents: The Maternal—Fetal Perspective 1093C. Gedeon, F. Garcia Bournissen and G. Koren48. History of Antipsychotic Drug Development 1111Shankar S. Gollapudi and Rajan Radhakrishnan49. Radiopharmaceuticals and Medical Imaging: Development of Radioimmumoconjugates for Radioimmunoimaging and Radioimmunotherapy of Malignant Diseases 1137Gang Niu and Xiaoyuan Chen50. Therapeutic Drug Development for Kidney Diseases 1159Mitchell H. Rosner, Joshua King, and Peter Monteleone51. Targeting Chemokines and Angiogenesis in Arthritis 1185Zoltan Szekaneez and Alisa E Koch52. Development of Therapeutic Agents: Methods and Approaches in the Development of Vaccines against Protozoan Parasites 1207Catherine Ivory and Kris Chadee53. Toxicology 1221John H. Duffus54. The Development of Phosphodiesterase 4 Inhibitors for Allergic and Nonallergic Infl ammatory Diseases of the Airways 1233Mark A. GiembyczINDEX 1251