Gene expression profiling in the discovery, optimization and development of novel drugs: one universal screening platform

被引:16
作者
Bol, D [1 ]
Ebner, R [1 ]
机构
[1] Avalon Pharmaceut Inc, Germantown, MD 20876 USA
关键词
chemical genetics; forward chemical genomics; high-throughput screening; microarray; transcriptional profiling;
D O I
10.2217/14622416.7.2.227
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
With recent advances in robotics and high-content screening and analysis methods, transcriptional profiling can now be utilized as a comprehensive forward chemical genomics platform for drug discovery, lead selection and lead optimization. It can be used to define the state of a cell on the basis of gene networks, and to search for drugs that can shift cellular states in a manner predicted at the genome level to be therapeutically beneficial. The treatment of cells with compounds produces transcriptional 'fingerprints' that reveal mechanism-of-action, and enable discrimination between individual compounds based on drug behaviors important to all phases of drug discovery and development.
引用
收藏
页码:227 / 235
页数:9
相关论文
共 56 条
[1]
Prediction of drug sensitivity and drug resistance in cancer by transcriptional and proteomic profiling [J].
Alaoui-Jamali, MA ;
Dupré, I ;
Qiang, H .
DRUG RESISTANCE UPDATES, 2004, 7 (4-5) :245-255
[2]
Protein-protein interactions and cancer: small molecules going in for the kill [J].
Arkin, M .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2005, 9 (03) :317-324
[3]
AUGUSTUS M, 2005, J CLIN LIGAND ASSAY, P285
[4]
Pharmacogenomic analysis: Correlating molecular substructure classes with microarray gene expression data [J].
Blower P.E. ;
Yang C. ;
Fligner M.A. ;
Verducci J.S. ;
Yu L. ;
Richman S. ;
Weinstein J.N. .
The Pharmacogenomics Journal, 2002, 2 (4) :259-271
[5]
BOL DK, 2003, CURRENT DRUG DISCOVE, P17
[6]
Using genome-wide transcriptional profiling to elucidate small-molecule mechanism [J].
Butcher, RA ;
Schreiber, SL .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2005, 9 (01) :25-30
[7]
Chan Y, 2005, NAT MED, V11, P102, DOI 10.1038/nm0105-102b
[8]
Wnt signaling to β-catenin involves two interactive components -: Glycogen synthase kinase-3β inhibition and activation of protein kinase C [J].
Chen, RH ;
Ding, WV ;
McCormick, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (23) :17894-17899
[9]
β-catenin-mediated signaling:: a molecular target for early chemopreventive intervention [J].
Clapper, ML ;
Coudry, J ;
Chang, WCL .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2004, 555 (1-2) :97-105
[10]
Clements Wilson M, 2003, Clin Colorectal Cancer, V3, P113, DOI 10.3816/CCC.2003.n.018