Rediscovering the sweet spot in drug discovery

被引:137
作者
Brown, D [1 ]
Superti-Furga, G [1 ]
机构
[1] Cellzome AG, Elstree WD6 3SH, Herts, England
关键词
PROTEIN-PROTEIN INTERACTIONS; SIGNAL-TRANSDUCTION; MASS-SPECTROMETRY; PROTEOMICS; TARGETS; COMPLEXES; IDENTIFICATION; PURIFICATION; ORGANIZATION; INHIBITORS;
D O I
10.1016/S1359-6446(03)02902-7
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Advances over the past decade in drug discovery technologies have not yet led to an increase in productivity. We analyzed the reasons that have led to this juncture and identify the selection of the right target and the right lead as crucial. New approaches are required to take full advantage of the genomics revolution. For targets, methods are becoming available for high-throughput proteome analysis and pathway characterization that synergize with studies of disease association and differential expression. For leads, methods are being developed that 'reverse' the high-throughput screening paradigm by mapping drugs and drug-like compounds back onto the proteome. The synergy between pathway mapping and compound mapping could allow the pharmaceutical and biotechnology industries to rediscover the sweet spot of research productivity.
引用
收藏
页码:1067 / 1077
页数:11
相关论文
共 42 条
[11]
Mechanisms of disease: Mitochondrial respiratory-chain diseases [J].
DiMauro, S ;
Schon, EA .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (26) :2656-2668
[12]
Ding S, 2003, P NATL ACAD SCI USA, V100, P7632, DOI 10.1073/pnas.0732087100
[13]
Global approaches to protein-protein interactions [J].
Drewes, G ;
Bouwmeester, T .
CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (02) :199-205
[14]
Strategic trends in the drug industry [J].
Drews, J .
DRUG DISCOVERY TODAY, 2003, 8 (09) :411-420
[15]
Drug discovery: A historical perspective [J].
Drews, J .
SCIENCE, 2000, 287 (5460) :1960-1964
[16]
Figeys D, 2002, ANAL CHEM, V74, p413A
[17]
Functional organization of the yeast proteome by systematic analysis of protein complexes [J].
Gavin, AC ;
Bösche, M ;
Krause, R ;
Grandi, P ;
Marzioch, M ;
Bauer, A ;
Schultz, J ;
Rick, JM ;
Michon, AM ;
Cruciat, CM ;
Remor, M ;
Höfert, C ;
Schelder, M ;
Brajenovic, M ;
Ruffner, H ;
Merino, A ;
Klein, K ;
Hudak, M ;
Dickson, D ;
Rudi, T ;
Gnau, V ;
Bauch, A ;
Bastuck, S ;
Huhse, B ;
Leutwein, C ;
Heurtier, MA ;
Copley, RR ;
Edelmann, A ;
Querfurth, E ;
Rybin, V ;
Drewes, G ;
Raida, M ;
Bouwmeester, T ;
Bork, P ;
Seraphin, B ;
Kuster, B ;
Neubauer, G ;
Superti-Furga, G .
NATURE, 2002, 415 (6868) :141-147
[18]
Protein complexes and proteome organization from yeast to man [J].
Gavin, AC ;
Superti-Furga, G .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2003, 7 (01) :21-27
[19]
Discovery of novel targets of quinoline drugs in the human purine binding proteome [J].
Graves, PR ;
Kwiek, JJ ;
Fadden, P ;
Ray, R ;
Hardeman, K ;
Coley, AM ;
Foley, M ;
Haystead, TAJ .
MOLECULAR PHARMACOLOGY, 2002, 62 (06) :1364-1372
[20]
Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders [J].
Hamosh, A ;
Scott, AF ;
Amberger, J ;
Bocchini, C ;
Valle, D ;
McKusick, VA .
NUCLEIC ACIDS RESEARCH, 2002, 30 (01) :52-55