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PREFACE ix CONTRIBUTORS xi PART I FUNDAMENTAL CONCEPTS 1 1. Current Needs for New Therapeutic Agents and Discovery Strategies???A Systems Pharmacology Approach 3 Sophie C. Desbiens and David H. Farb 2. Target Selection in Drug Discovery 25 Charles F. Albright 3. New Drug Applications 35 John S. McInnes and Donald O. Beers 4. From Concept to the Clinics: Development of Cancer Therapeutics 47 Balveen Kaur, Gregory B. Lesinski, and Abhik Ray Chaudhary 5. Development of Countermeasures for Bioterrorism in the United States 73 Gregory H. Levine and Jeffrey I. Handwerker 6. Development and Application of Conformation–Selective Integrin Antibodies 91 Nathan S. Astrof, Dan Peer, and Motomu Shimaoka 7. Pain Management Market Overview 113 Anita Holdcroft 8. Antiviral Market Overview 127 Anita Arora, Natalia Mendoza, and Stephen K. Tyring PART II METHODS AND TECHNIQUES IN DRUG DISCOVERY AND DEVELOPMENT 145 9. High–Throughput Screening for Small–Molecule Drug Discovery 147 C. Parker and J.–H. Zhang 10. Mass Spectrometry 181 Robert D. English and Anthony M. Haag 11. Molecular Screening for Therapeutic Agents 207 R. Damoiseaux 12. Accelerator Mass Spectrometry and Positron Emission Tomography in Human Microdosing 241 Zhengdong Cheng 13. Development of Antimicrobial Peptides as Therapeutic Agents 285 Robert S. Hodges, Ziqing Jiang, James Whitehurst, and Colin T. Mant 14. Antibodies for Human Diseases 359 Guo–Liang Yu and Jian Ni 15. Combinatorial Compounds and Drug Discovery 399 James C. Bigelow 16. Locoregional Chemoradiotherapy of Cancer Using Hydrogel 413 David J. Yang, Ali Azhdarinia, Hiroaki Kurihara, and E. Edmund Kim 17. RNAi–Mediated Therapeutics 425 Nuria Morral and Scott R. Witting 18. Crystallography 445 Carl H. Schwalbe 19. PEGylation 463 Sanju Dhawan, Deepak N. Kapoor, Rishi Kapil, Mano Kumarj, and Ankur Bansal 20. Gold Standard Animal Models 517 Carol Casteneda and Michael S. LaPointe 21. Discovery of Vaccine Adjuvants 533 Fiona A. Sharp and Ed C. Lavelle 22. Oral Delivery of Macromolecules for the Development of Therapeutic Agents 547 Hye J. Lee and Chanmi Choi 23. Aerosol Drug Delivery to the Lungs 565 Andrew R. Martin and Warren H. Finlay 24. Resistance to Antiplatelet Theraphy 589 Paul A. Gurbel, Udaya S. Tantry, and Mark J. Antonino 25. Antibiotic Development 611 Robert L. Bettiker and Jason C. Gallagher PART III THERAPEUTIC TOPICS 629 26. Antimicrobial Resistance in Biofi lms: A Sticky Situation 631 Shu Yeong Queck and Michael Otto 27. Drotrecogin Alfa Activated (Recombinant Human Activated Protein C, Xigris) 645 Byungse Suh and Rafi k Samuel 28. Anti–Inflammatory Therapeutics 655 Marion M. Chan and Dunne Fong 29. Anti–Inflammatory/Analgesics: An In–depth Look at p38 MAP Kinases 673 Kelly L. Brown 30. Cardiovascular Disease: In–Depth Look 707 Nicholas B. Norgard and Mazen Abu–Fadel 31. Ezetimibe and Cholesterol Absorption 723 Stefan Oswald and Werner Siegmund 32. Cardiology???In–Depth Look: Kinases as Therapeutic Targets in the Heart 743 Karin Mauer and J. Emilio Exaire 33. Statins in the Reduction of Cardiovascular Events 773 Rajesh Sachdeva, Bradley Hughes, and Jawahar L. Mehta 34. Cardiology???In–Depth Look: Advances in Antiplatelet Theraphy 785 Karin Mauer and Jorge F. Saucedo 35. Gastrointestinal Disorders: A Focus on Acid–Suppressive Agents 813 Brian Hemstreet 36. Pharmacology of Vasopressin and the Renin???Angiotension???Aldosterone System 825 Elizabeth J. Brant and Julian L. Seifter 37. New Drugs and Nutaceutical in the Treatment of Osteoarthristis 847 Y. Henrotin and J. Y. Reginster 38. Development of Anticytokine Agents for Rheumatoid Arthritis 881 Jonathan Sherlock, Christopher D. Buckley, and Karim Raza 39. Overview of CNS Neuropharmaceuticals 897 Tauser Roxana–Georgiana and Antohe Dan–Stefan 40. Thinking Outside the Box in Alzheimer Disease Treatment 929 Rudy J. Castellani, Michael W. Marlatt, Akihiko Nunomura, Paula I. Moreira, Hyoung–Gon Lee, Gemma Casadesus, Xiogwei Zhu, George Perry, and Mark A, Smith 41. Neurotrophic Factors as Novel Therapeutic Targets 943 Stephen D. Skaper 42. Oncology 963 Arkadiusz Z. Dudek and Steven F. Powell 43. Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia 999 Muhammad Mansoor Alam and Moshe Talpaz 44. Aromatase Inhibitors for Breast Cancer 1011 Akm Hossain and Jame Abraham 45. Evolution of Selective Estrogen and Androgen Receptor Modulators: Status of Current Therapy and New Drug Development 1019 Gregory T. Wurz and Michael W. DeGregorio 46. In–Depth Look: anti–TNF–?? Therapies 1045 Satadal Chatterjee and Shobhan Gaddameedhi 47. Development of Therapeutic Agents: The Maternal???Fetal Perspective 1093 C. Gedeon, F. Garcia Bournissen and G. Koren 48. History of Antipsychotic Drug Development 1111 Shankar S. Gollapudi and Rajan Radhakrishnan 49. Radiopharmaceuticals and Medical Imaging: Development of Radioimmumoconjugates for Radioimmunoimaging and Radioimmunotherapy of Malignant Diseases 1137 Gang Niu and Xiaoyuan Chen 50. Therapeutic Drug Development for Kidney Diseases 1159 Mitchell H. Rosner, Joshua King, and Peter Monteleone 51. Targeting Chemokines and Angiogenesis in Arthritis 1185 Zoltan Szekaneez and Alisa E Koch 52. Development of Therapeutic Agents: Methods and Approaches in the Development of Vaccines against Protozoan Parasites 1207 Catherine Ivory and Kris Chadee 53. Toxicology 1221 John H. Duffus 54. The Development of Phosphodiesterase 4 Inhibitors for Allergic and Nonallergic Infl ammatory Diseases of the Airways 1233 Mark A. Giembycz INDEX 1251