Proteases as Targets for Therapy, Выпуск 146

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M. Abdel-Meguid, Klaus von der Helm, Bruce D. Korant, John Chris Dion Cheronis
Springer Science & Business Media, 2000 - Всего страниц: 410
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This volume is the first to combine latest information on viral, microbial and cellular proteolytic enzymes as potential targets for human therapeutics. Proteases control a large array of physiological reactions, and are involved in a variety of pathological processes for which effective medications are currently needed and/or being sought after. Although protease inhibitors have been investigated for many years, few have been employed therapeutically. Recent break- through by HIV protease inhibitors as therapeutic drugs has re-encouraged the search for inhibitors of other proteolytic enzymes. Klaus von der Helm, who described the first viral protease has brought leading experts together to discuss not only the success and problems of clinical use and continuing prospects, but to review further potential drug targets. This volume provides detailed information and evaluations of key viral, bacterial, fungal, and cellular proteases as potential future drug candidates.

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Содержание

TANAKA K The Tokyo Metropolitan Institute of Medical Science
3
Early Clinical Studies
13
Clinical Experience with Human Immunodeficiency Virus Protease
23
References
30
Biochemical Basis for Resistance
38
References
44
Two Strategies to Reduce Viral Resistance to
50
Designing Drugs to Inhibit PIResistant Viruses
56
G Conclusions
231
38
232
75
234
39
240
Inhibitors of TACE and TNFα Secretion
245
41
255
CHAPTER 14
259
B Serine Elastases and Inflammation
262

Suggestions for Future Therapeutic Strategies
66
CHAPTER 5
75
The NS23 Proteinase
87
CHAPTER 6
95
Substrates
105
References
111
CHAPTER 7
117
E The 3C Proteinases
125
F Inhibition of 3C Proteinases
132
222
140
CHAPTER 8
145
535335
147
25
148
Potential InhibitorBinding Sites
152
E Summary and Prospects
155
27
157
E Paradigms for Testing Proteinase Inhibitors as Therapeutic
173
F Bacterial Proteinases to the Rescue
179
56
183
CHAPTER 10
189
Serine Proteases
198
CHAPTER 11
207
Section Overview
213
33
218
CHAPTER 12
221
General Considerations in the Development of MMPIS
224
Potential Clinical Targets for SerineElastase Inhibition
268
44
269
78
275
CHAPTER 15
277
FactorXa Inhibitors
289
CHAPTER 16
301
80
303
Cystatins in Cancer
310
Potential Transcriptional Regulation
316
49
324
81
325
CHAPTER 17
329
G Potential for Caspase Inhibitor Therapy
335
82
339
CHAPTER 18
341
Regulatory Control of Ub and the Proteasome in Apoptosis
346
F The UbProteasome System and Cancer Therapy
353
84
355
51
358
CHAPTER 19
359
References
370
Role of Mutant Presenilins in Amyloid Generation
378
E Proteolytic Degradation of PSs
384
New Targets for AntiAmyloidogenic Drugs?
390
Subject Index
403
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