Combinatorial chemistry. Facing the challenge of chemical genomics

被引:14
作者
Darvas, F
Dorman, G
Urge, L
Szabo, I
Ronai, Z
Sasvari-Szekely, M
机构
[1] ComGenex Inc, H-1027 Budapest, Hungary
[2] Semmelweis Univ, Sch Med, Inst Med Chem Mol Biol & Pathobiochem, H-1088 Budapest, Hungary
关键词
D O I
10.1351/pac200173091487
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
In the age of high-throughput screening and combinatorial chemistry, the focus of drug discovery is to replace the sequential approach with the most effective parallel approach. By the completion of the human gene-map, understanding and healing a disease require the integration of genomics, proteomics, and, very recently, metabolornics with early utilization of diverse small-molecule libraries to create a more powerful "total" drug discovery approach. In this post-genomic era, there is an enhanced demand for information-enriched combinatorial libraries which are high-quality, chemically and physiologically stable, diverse, and supported by measured and predicted data. Furthermore, specific marker libraries could be used for early functional profiling of the genome, proteome, and metabolome. In this new operating model, called "combinatorial chemical genomics", an optimal combination of the marker and high-quality libraries provides a novel synergy for the drug discovery process at a very early stage.
引用
收藏
页码:1487 / 1498
页数:12
相关论文
共 18 条
[1]   Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking [J].
Benjamin, J ;
Li, L ;
Patterson, C ;
Greenberg, BD ;
Murphy, DL ;
Hamer, DH .
NATURE GENETICS, 1996, 12 (01) :81-84
[2]  
DARVAS F, 2001, S MOL INF COMB QUANT
[3]  
DARVAS F, COMBINATORIAL CHEM
[4]  
DARVAS F, 1977, HIGH THROUGHPUT SCRE, P223
[5]  
DORMAN G, 2001, CURR DRUG DISC, P21
[6]   Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking [J].
Ebstein, RP ;
Novick, O ;
Umansky, R ;
Priel, B ;
Osher, Y ;
Blaine, D ;
Bennett, ER ;
Nemanov, L ;
Katz, M ;
Belmaker, RH .
NATURE GENETICS, 1996, 12 (01) :78-80
[7]  
Faraone SV, 1999, AM J PSYCHIAT, V156, P768
[8]   Rapid and general profiling of protease specificity by using combinatorial fluorogenic substrate libraries [J].
Harris, JL ;
Backes, BJ ;
Leonetti, F ;
Mahrus, S ;
Ellman, JA ;
Craik, CS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (14) :7754-7759
[9]  
HAYSTEAD TAJ, 2001, CURR DRUG DISCO 0322
[10]   ADMET - turning chemicals into drugs [J].
Hodgson, J .
NATURE BIOTECHNOLOGY, 2001, 19 (08) :722-726