Integrated drug discovery technologies PDF
Preview Integrated drug discovery technologies
Integrated Drug Discovery Technologies edited by Houng-yau Mei Rubicon Genomics, Inc. Ann Arbor, Michigan Anthony W. Czarnik Sensors for Medicine and Science, Inc. Germantown, Maryland MARCEL - MARCEDL EKKERIN, C. NEWY ORK BASEL DEKKER Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved. ISBN:0-8247-0649-8 This book is printed on acid-free paper. Headquarters Marcel Dekker,Inc. 270 Madison Avenue,New York,NY 10016 tel:212-696-9000; fax:212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4,Postfach 812,CH-4001 Basel,Switzerland tel:41-61-261-8482; fax:41-61-261-8896 World Wide Web http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means,electronic or mechanical,including photocopying,microfilming,and recording,or by any information storage and retrieval system,without permission in writing from the publisher. Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved. Preface We scientists in the drug discovery business are not so different from alchemists of old: “Convert this lead into gold and I shall share my wealth with you.” Or perhaps, “Convert this lead into gold or else!”You’ve no doubt felt motivation from both the carrot and the stick during your career,but it probably sounded more like this: “If you can make a better COX-2 inhibitor, the company’s stock will triple!” Or, “If we don’t fill our pipeline quickly, someone is going to buy us!” Whether then or now,the risk/reward ratio is literally a step function,not a con- tinuum, dependent on a scientist accomplishing a mission his analytical con- science cannot guarantee. Now,as in earlier times,we try anything that makes sense in the discovery process. Because no one method has provided a “lock”on discovery,scientists have room for style and intuition. “I know the value of computer-aided drug design.” “The more times you’re up at bat,the more often you’ll hit a home run— so screen.” “Drug discovery requires a genomic/proteomic/metabolic pathway approach.” “Start with someone else’s drug and synthesize around the patent.”Who’s right? It begins to sound like a debate of the merits of one religion versus another. But sci- ence is about quantitation; why can’t we simply calculate which approach is the best? Perhaps because no one does “outcomes research” on the drug discovery process. I think instead it is because science is ultimately a human endeavor,and each person espousing a discovery philosophy is motivated to make that choice look like the right one. In the marketplace of ideas,steak sells,and sizzle sells. Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved. This book is about steak. If you hear a little sizzle as well,it’s because the authors believe passionately in their technology and the philosophy that accom- panies it. “Lead into gold,” each plaintively wails. Lead, gold, carrots, sticks, steak,sizzle,and drugs. Let the games begin. Anthony W. Czarnik Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved. Contents Preface Contributors INTRODUCTION 1. The Motivation:A Top-Down View Wendell Wierenga PART I. FROM GENE TO SCREEN 2. Target Identification and Validation:Coupling Genotype to Phenotype Gary McMaster 3. Functional Genomics David O’Hagan 4. Integrated Proteomics Technologies Joseph A. Loo,James A. Blackledge,Ping Du,Greg W. Kilby, Robert A. Lepley,Joseph Macri,Rachel R. Ogorzalek Loo, Stephen T. Rapundalo,and Tracy I. Stevenson Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved. 5. Where Science Meets Silicon:Microfabrication Techniques and Their Scientific Applications Tony J. Beugelsdijk 6. SNP Scoring for Drug Discovery Applications John P. Nolan,P. Scott White,and Hong Cai 7. Protein Display Chips Tina S. Morris 8. Integrated Proteomics Technologies and In Vivo Validation of Molecular Targets Christian Rohlff PART II. HIGH-THROUGHPUT SCREENING 9. High-Throughput Screening as a Discovery Resource John P. Devlin 10. Fluorescence Correlation Spectroscopy (FCS) and FCS-Related Confocal Fluorimetric Methods (FCS+plus):Multiple Read-Out Options for Miniaturized Screening Cornelia Rufenach,Andreas Scheel,Sylvia Sterrer, and Rodney Turner 11. Homogeneous Time-Resolved Fluorescence Loraine V. Upham,Jocelyn W. Burke,Betty Howard, and Gerard Mathis 12. ADME-Tox Screening in Drug Discovery Albert P. Li 13. Screening Lead Compounds in the Postgenomic Era: An Integrated Approach to Knowledge Building from Living Cells Kenneth A. Giuliano,Ravi Kapur,Keith R. Olson, Chandrasekaran Vasudevan,Jian Wang,and Elizabeth S. Woo 14. Miniaturization Technologies for High-Throughput Biology Walter D. Niles and Peter J. Coassin Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved. 15. Data Management for High-Throughput Screening Lee Amon PART III. HIGH-THROUGHPUT CHEMISTRY 16. Combinatorial Chemistry:The History and the Basics Michal Lebl 17. New Synthetic Methodologies Tasir S. Haque,Andrew P. Combs,and Lorin A. Thompson 18. Supports for Solid-Phase Synthesis Christophe Fromont,Vincent Pomel,and Mark Bradley 19. The NMR “Toolkit”for Compound Characterization Paul A. Keifer 20. Materials Management David A. Kniaz Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved. Contributors Lee Amon MarketQwest Associates,Fremont,California Tony J. Beugelsdijk, Ph.D. Los Alamos National Laboratory, Los Alamos, New Mexico James A. Blackledge Department of Discovery Technologies, Pfizer Global Research and Development,Ann Arbor,Michigan Mark Bradley, Ph.D. Department of Chemistry, University of Southampton, Southampton,United Kingdom Jocelyn W. Burke, Ph.D. Department of BioChipventures, Packard Bio- Science,Meriden,Connecticut Hong Cai BioScience Division,Los Alamos National Laboratory,Los Alamos, New Mexico Peter J. Coassin Department of Instrumentation Research and Development, Aurora Biosciences Corporation,San Diego,California Andrew P. Combs, Ph.D. Directed Parallel Synthesis Group, Bristol-Myers Squibb Company,Wilmington,Delaware Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved. x Contributors Anthony W. Czarnik,Ph.D. Chief Scientific Officer,Sensors for Medicine and Science,Inc.,Germantown,Maryland John P. Devlin, Ph.D. MicroSource Discovery Systems, Inc., Gaylordsville, Connecticut Ping Du Department of Discovery Technologies, Pfizer Global Research and Development,Ann Arbor,Michigan Christophe Fromont,Ph.D. Ribo Targets Ltd.,Cambridge,United Kingdom Kenneth A. Giuliano, Ph.D. Department of Assay Development, Cellomics, Inc.,Pittsburgh,Pennsylvania Tasir S. Haque, Ph.D. Directed Parallel Synthesis Group, Bristol-Myers Squibb Company,Wilmington,Delaware Betty Howard, M.S. Microplate Detection Systems, Packard BioScience, Downers Grove,Illinois Ravi Kapur, Ph.D. CellChip Department, Cellomics, Inc., Pittsburgh, Pennsylvania Paul A. Keifer,Ph.D. CST Associates,Omaha,Nebraska Greg W. Kilby Department of Discovery Technologies,Pfizer Global Research and Development,Ann Arbor,Michigan David A. Kniaz, B.S., M.B.A. Product Development, SciQuest Inc., Newton Square,Pennsylvania Michal Lebl, Ph.D., D.Sc. High Throughput Synthesis Department, Illumina, Inc.,San Diego,California Robert A. Lepley, Ph.D.* Department of Discovery Technologies, Pfizer Global Research and Development,Ann Arbor,Michigan Albert P. Li,Ph.D. In Vitro Technologies,Inc.,Baltimore,Maryland Joseph A. Loo, Ph.D. Department of Discovery Technologies, Pfizer Global Research and Development,Ann Arbor,Michigan *Current affiliation:TIS Group,Minneapolis,Minnesota Copyright ©2002 by Marcel Dekker,Inc. All Rights Reserved.
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