Model Organisms in Drug Discovery

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xii LIST OF CONTRIBUTORS Titus Kaletta Devgen NV, Technologiepark 9, B-9052 Ghent-Zwijnaarde, Belgium Francis Kern Lexicon Genetics Incorporated, 8800 Technology Forest Place, The Woodlands, TX 77381, USA Rachel Kindt Exelixis, Inc., 170 Harbor Way, South San Francisco, CA 94083-0511, USA Thomas Lanthorn Lexicon Genetics Incorporated, 8800 Technology Forest Place, The Woodlands, TX 77381, USA Hao Li Department of Functional Genomics, Novartis Pharmaceuticals Corporation, 556 Morrive Avenue, SEF2026, Summit, NJ 07901, USA Geert Mudde Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, D- 82152 Martinsried, Germany Michael Nehls Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, D- 82152 Martinsried, Germany Tamas Oravecz Lexicon Genetics Incorporated, 8800 Technology Forest Place, The Woodlands, TX 77381, USA Michael Pack Departments of Medicine and Cell and Developmental Biology, University of Pennsylvania School of Medicine, Room 1212 BRB 2/3, 421 Curie Blvd., Philadelphia, PA 19104, USA James Piggott Lexicon Genetics Incorporated, 8800 Technology Forest Place, The Woodlands, TX 77381, USA David Powell Lexicon Genetics Incorporated, 8800 Technology Forest Place, The Woodlands, TX 77381, USA Ramiro Ramirez-Solis Lexicon Genetics Incorporated, 8800 Technology Forest Place, The Woodlands, TX 77381, USA Petra Ross-Macdonald Department of Applied Genomics, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, PO Box 5400, Princeton, NJ 08543, USA Andreas Russ Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, D- 82152 Martinsried, Germany Arthur T. Sands Lexicon Genetics Incorporated, 8800 Technology Forest Place, The Woodlands, TX 77381, USA Andreas Schröder Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, D- 82152 Martinsried, Germany
LIST OF CONTRIBUTORS xiii Stefan Schulte-Merker Exelixis, Deutschland GmbH, Spemannstrasse 35, D-72076, Tu¨bingen, Germany Corina Schütt The Genetics Company, Inc., Wagistrasse 27, CH-8952 Zu¨rich-Schlieren, Switzerland Reinhard Sedlmeier Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, D-82152 Martinsried, Germany Gabriele Stumm Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, D- 82152 Martinsried, Germany Sigrid Wattler Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, D- 82152 Martinsried, Germany Brian Zambrowicz Lexicon Genetics Incorporated, 8800 Technology Forest Place, The Woodlands, TX 77381, USA
Page 1 and 2: Model Organisms in Drug Discovery M
Page 3 and 4: Copyright u 2003 John Wiley & Sons
Page 5 and 6: Contents List of contributors .....
Page 7 and 8: CONTENTS ix 7 Genetics and Genomics
Page 9: List of Contributors Hector Beltran
Page 13 and 14: 1 Introduction to Model Systems in
Page 15 and 16: Organism INTEGRATING MODEL ORGANISM
Page 17 and 18: INTEGRATING MODEL ORGANISM RESEARCH
Page 19 and 20: INTEGRATING MODEL ORGANISM RESEARCH
Page 21 and 22: 10 GROWING YEAST FOR FUN AND PROFIT
Page 51 and 52: 3 Caenorhabditis elegans Functional
Page 53 and 54: THE DRUG DISCOVERY PROCESS 43 thoug
Page 55 and 56: multivulva phenotype of Ras gain-of
Page 57 and 58: disease. These molecular targets ar
Page 59 and 60: FROM DISEASE TO TARGET 49 Figure 3.
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FROM DISEASE TO TARGET 51 Figure 3.
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signaling pathway. The third catego
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FROM DISEASE TO TARGET 55 resistant
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phenomenon was first observed in C.
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profiles. The C. elegans gene expre
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emerging technologies. Forward gene
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The compound library LEAD DISCOVERY
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LEAD DISCOVERY 65 previous section,
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LEAD DISCOVERY 67 Figure 3.5 Distri
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Compound learning set for assay val
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10 000-15 000 human drug targets ar
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transporter itself. The SSRIs that
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REFERENCES 75 de Montigny, C., Blie
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REFERENCES 77 Lewis, J. A., Wu, C.
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REFERENCES 79 Tissenbaum, H. A. and
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82 DROSOPHILA AS A TOOL FOR DRUG DI
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100 DROSOPHILA AS A TOOL FOR DRUG D
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5 Drosophila - a Model System for T
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EVOLUTIONARY CONSERVATION OF DISEAS
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TARGET IDENTIFICATION/TARGET VALIDA
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CHEMICAL GENETICS 143 acid identity
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3. A hit identifies a biologically
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about their function in a multicell
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REFERENCES 149 Han, Z. S., Enslen,
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REFERENCES 151 Rintelen, F., Stocke
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6 Mechanism of Action in Model Orga
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INTRODUCTION TO COMPOUND DEVELOPMEN
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MODEL ORGANISMS ARRIVE ON THE SCENE
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ELUCIDATING THE MECHANISM OF COMPOU
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ELUCIDATING THE MECHANISM OF COMPOU
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A CASE STUDY FOR ALZHEIMER’S DISE
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NEW CHEMICAL GENETIC STRATEGIES 171
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A CASE STUDY FOR INNATE IMMUNITY 17
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GLOBAL GENE EXPRESSION STUDIES IN M
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As described above, the extensive i
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REFERENCES 179 Austin, J. and Kimbl
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REFERENCES 181 Hughes, T. R., Marto
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REFERENCES 183 Sin, N., Meng, L., W
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186 GENETICS AND GENOMICS IN THE ZE
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8 Lipid Metabolism and Signaling in
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FISH AS A MODEL ORGANISM 205 genes
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LIPID METABOLISM SCREEN 207 transpo
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LIPID METABOLISM SCREEN 209 Figure
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the embryo media containing radioac
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ZEBRAFISH AS A MODEL SYSTEM 213 Fig
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ZEBRAFISH AS A MODEL SYSTEM 215 Reg
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aspirin, which has potent inhibitor
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REFERENCES 219 Chau, I. and Cunning
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REFERENCES 221 Patrono, C., Patrign
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224 CHEMICAL MUTAGENESIS IN THE MOU
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252 SATURATION SCREENING OF DRUGGAB
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280 INDEX bupropion 92 busulfan 143
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282 INDEX Dscam 171 dual-energy X-r
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284 INDEX L-685,818 16 lead discove
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286 INDEX protein function 19-22 pr
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288 INDEX yeast (continued) functio
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