Development of Therapeutic Agents Handbook

A comprehensive look at current drug discovery and developmentmethods and the roadmap for the future

Providing both understanding and guidance in characterizingpotential drugs and their production and synthesis, Developmentof Therapeutic Agents Handbook gives professionals a basic toolto facilitate research and development within this challengingprocess. This comprehensive text brings together, in one resource,a compendium of concepts, approaches, methodologies, andlimitations that need to be considered in the formulation oftherapeutic agents across a range of therapeutic fields. Both areference and a call to action for the pharmaceutical industry,Development of Therapeutic Agents Handbook examines recentinnovations taking shape in the various medical disciplinesinvolved in drug discovery, and shows why these advances need to beembraced universally among researchers to improve their solutionstrategies. Additional subject matter includes:

Extensive coverage and in–depth look into novel treatments andtherapeutics

Discussion of hot topics like new drugs and nutraceuticals, thediscovery and development of vaccines, cancer therapeutics, andmarket overviews

Coverage of therapeutic drug development for specific diseaseareas, such as cardiology, oncology, breast cancer, and kidneydiseases

As research in biology, chemistry, medicine, and technologyrapidly progresses, it is becoming increasingly important formedical researchers to maintain an up–to–date knowledge base ofemerging trends directing promising new therapies. Developmentof Therapeutic Agents Handbook serves this purpose, acting asboth a one–stop reference rich in valid science, and a tool tocarve out new pathways in the pursuit of bringing safer and moreeffective drugs to the marketplace.

PREFACE ix

CONTRIBUTORS xi

PART I FUNDAMENTAL CONCEPTS 1

1. Current Needs for New Therapeutic Agents and DiscoveryStrategies 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 CancerTherapeutics 47
Balveen Kaur, Gregory B. Lesinski, and Abhik RayChaudhary

5. Development of Countermeasures for Bioterrorism in the UnitedStates 73
Gregory H. Levine and Jeffrey I. Handwerker

6. Development and Application of Conformation–SelectiveIntegrin 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 ANDDEVELOPMENT 145

9. High–Throughput Screening for Small–Molecule Drug Discovery147
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 EmissionTomography in Human Microdosing 241
Zhengdong Cheng

13. Development of Antimicrobial Peptides as Therapeutic Agents285
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 Hydrogel413
David J. Yang, Ali Azhdarinia, Hiroaki Kurihara, and E. EdmundKim

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, andAnkur 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 ofTherapeutic 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 Situation631
Shu Yeong Queck and Michael Otto

27. Drotrecogin Alfa Activated (Recombinant Human ActivatedProtein 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 MAPKinases 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 TherapeuticTargets 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 AntiplateletTheraphy 785
Karin Mauer and Jorge F. Saucedo

35. Gastrointestinal Disorders: A Focus on Acid–SuppressiveAgents 813
Brian Hemstreet

36. Pharmacology of Vasopressin and theRenin Angiotension Aldosterone System 825
Elizabeth J. Brant and Julian L. Seifter

37. New Drugs and Nutaceutical in the Treatment ofOsteoarthristis 847
Y. Henrotin and J. Y. Reginster

38. Development of Anticytokine Agents for Rheumatoid Arthritis881
Jonathan Sherlock, Christopher D. Buckley, and KarimRaza

39. Overview of CNS Neuropharmaceuticals 897
Tauser Roxana–Georgiana and Antohe Dan–Stefan

40. Thinking Outside the Box in Alzheimer Disease Treatment929
Rudy J. Castellani, Michael W. Marlatt, Akihiko Nunomura, PaulaI. Moreira, Hyoung–Gon Lee, Gemma Casadesus, Xiogwei Zhu, GeorgePerry, 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 Leukemia999
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 ReceptorModulators: Status of Current Therapy and New Drug Development1019
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 FetalPerspective 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 ofRadioimmumoconjugates for Radioimmunoimaging and Radioimmunotherapyof 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 Arthritis1185
Zoltan Szekaneez and Alisa E Koch

52. Development of Therapeutic Agents: Methods and Approaches inthe 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 forAllergic and Nonallergic Infl ammatory Diseases of the Airways1233
Mark A. Giembycz

INDEX 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 extensivereferences.   (Book News, 1 April 2012)