Molecular Pathomechanisms and New Trends in Drug Research

Transcription

1 Molecular Pathomechanisms and New Trends in Drug Research Edited by Gyorgy Keri and Istvan Toth Taylor & Francis Taylor &. francis Group LONDON AND NEW YORK

2 Contents List of contributors Acknowledgments Aims and scope xi xv xvii PART I Introduction I 1 Introduction - a breakthrough in modern drug research 3 GYORGY KERI AND ISTVAN TOTH PART 2 Pathomechanisms and molecular target finding 5 2 Drug discovery based on functional genomics - target selection and validation 7 GABOR M1KA1.A, ISTVAN VALYI-NAGY 3 Mapping of the human genome 19 ZOLTAN L. MARCSEK AND EUGENE R. ZABAROVSKY 4 Molecular diagnosis of signal transduction related diseases 39 ISTVAN EMBER AND ISTVAN KISS PART 3 Common pathway and general mechanism 51 5 Signal transduction therapy 53 ALEXANDER I.EVITZKI 6 Heat shock proteins 67 PETER CSERMELY AND ICHIRO YAHARA 7 Transcription factors as targets for drug development 76 DEVARAJAN KARUNAGARAX AND BHARAT B. AGGARWAI. 8 Apoptosis in various diseases 92 BELA SZENDE 9 Caspases - the regulators and executioners of the apoptotic process 100 PAl. I. BAUER, ERZSEBET KENESI AND ANDRAS ILEES

3 viii Contents 10 The role of drug metabolism enzymes in signal transduction processes 110 JOZSEFMANDL 11 Recent developments in calcium signaling - implications for disease and drug development 114 GREG MONTEITH 12 T-cell receptors and coreceptors; cytokine receptors 120 ANDRASFALLS 13 Neuro-immune responses in different diseases role of tumor necrosis factor-a and IL-I 133 SZILYESZTER E. VIZI 14 Regulation of B lymphocyte function by crosstalk between receptors with stimulatory and inhibitory activity 139 JANOS GERGELY AND ANNA ERDEI PART 4 Drug discovery Combinatorial chemistry 151 ARPAD FLRKA 16 Lead search, selection and optimization in silico (virtual) screening 166 LASZLO ORFI AND ISTVAN KOVESDI 17 The development of carbohydrate based therapeutics 178 NICHOLAS DRINNAN AND TRACIE RAMSDALE 18 Introduction to structure and ligand-based drug design 191 GYORGY M. KESERU. II.D1KO MAGDO AND GABOR NARAY-SZABO 19 Gene therapy 203 LASZLO KOPPER PART 5 Molecular pathomechanism of cancer Cancer genetics 213 LASZLO KOPPER 21 Cancer as a communication disorder 227 GYORGY KERI AND AXEL ULLRICH PART 6 Infectious diseases Human immunodeficiency virus - pathogenesis, replication strategy and the role of an tire tro viral drugs 251

4 Contents ix 23 Signal transduction in virus infected cells implications for therapy 2(> 1 PETER KRAJCSI 24 The development of vaccines to prevent rheumatic fever COLLEEN OLIVE AND MICHAEL GOOD 25 Systemic antifungal agents 28 ] ROSS P. MCGEARY PART 7 Diseases of the central and the peripheral nervous system Mechanisms of neurodegenerative diseases 291 RICHARD ANTHONY HUGHES 27 Neurobiology of pain identification of novel targets for new pain management medications MAREE SMITH 28 Capsaicin receptors as target molecules on nociceptors for development of novel analgesic agents 319 JANOS SZOI.CSANY1 29 Migraine 331 ILONA JEI.ENCSIK AND CSABA ERTSEY 30 Regulatory mechanisms in focal ischemic stroke 350 ZOLTAN NAGY. MARTIN J. BERG AND NEVILLE MARKS 31 Signal transduction abnormalities in epilepsies 3b 1 PETER HAI.ASZ 32 Parkinson's disease its causes and treatment 37(> MICHAEL S. STARR 33 Physiological role of amyloid precursor protein (APP) and /3-amyloid peptides 387 B. I'LNKL AND I. HARKANY 34 Eye diseases tnj PIROSKA E. RAKOCZY. WT.I-YONG SHIN AND CHRIS. BARRY PART 8 Cardiovascular diseases Atherosclerosis 1! '< GLRD SCUM I I Z. MICHAEL I OR/.EW'.sKI. s I I.I \\ I! AR1.AG1 \\ 11 \\ MI I i, \\i, 1 ir( i (\ I K 36 Disorders of the blood coagulation - fibrinolytic system ll,'! RAYMUND MACHO\ K H

5 x Contents 37 Angiogenesis 465 JOZSEF TiMAR, BALAZS DOME AND SANDOR PAKU PART 9 Endocrinal and gastrointestinal disorders Diabetes and the heart 489 LINDSAY BROWN 39 The leptin hormonal system as a target for new drugs designed to control food intake and body weight 499 ANDREW CONSTANTI 40 Regulation of gastric secretion, Helicobacter pylori and inflammation of the gastric epithelium 513 LASZLO PRONAI, BELA MOLNAR AND ZSOLT TULASSAY 41 Osteoporosis 533 GYORGY MESZAROS, TAMAS KARDON AND GYULA POOR PART 10 Drug applications Modulation of drug effects by ABC transporters 545 GERGELY SZAKACS AND BALAZS SARKADI 43 Peptide or protein based drug delivery and targeting systems 553 FERENC HUDECZ, GYORGY KOCZAN ANDJUDIT REMENYI 44 Current approaches to peptidomimetics 579 MICHAEL J. KELSO AND DAVID P. FAIRLIE 45 Drug delivery systems utilizing lipids and sugars 599 ALLAN WONG, VERONIKA BENDER AND ISTVAN TOTH 46 Pharmacokinetic-pharmacodynamic modeling and an example of its application to drug delivery 613 EDWARD J. TRIGGS Author index Subject index 6 2 1