Pathway analysis software as a tool for drug target selection, prioritizatino and validation of drug mechanism

被引:19
作者
Sivachenko, Andrey Y. [1 ]
Yuryev, Anton [1 ]
机构
[1] Ariadne Genom Inc, Rockville, MD 20850 USA
关键词
biomolecular network; drug discovery; pathway analysis;
D O I
10.1517/14728222.11.3.411
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
One of the major challenges of drug discovery today is the poor understanding of the detailed molecular mechanisms underlying both disease progression and drug action. insufficient drug specificity and side effects are often discovered during the late stages of drug development, sometimes after the drug is released on the market. These discoveries result in a high target attrition rate, a slow drug design pipeline and high development costs. Recent advances in systems biology and pathway analysis can help make true rational design a reality through the integration of experimental observations with underlying cellular regulation and metabolic networks. It should enable the formulation of better and more informed testable hypotheses with regard to the most efficient target candidates. In this article, the authors overview the broad and heterogeneous field of molecular interaction databases and pathway analysis tools, and the challenges existing in the field. The authors describe and classify different approaches for data acquisition, storage and navigation, give a detailed description of the integrative technology behind the Pathway Studio (R) software solution, and present a comparison with other integrative pathway analysis platforms suitable for drug discovery tasks.
引用
收藏
页码:411 / 421
页数:11
相关论文
共 53 条
[21]  
Kanehisa M, 2002, NOVART FDN SYMP, V247, P91
[22]   Cardiotoxicity of the cancer therapeutic agent imatinib mesylate [J].
Kerkela, Risto ;
Grazette, Luanda ;
Yacobi, Rinat ;
Iliescu, Cezar ;
Patten, Richard ;
Beahm, Cara ;
Walters, Brian ;
Shevtsov, Sergei ;
Pesant, Stephanie ;
Clubb, Fred J. ;
Rosenzweig, Anthony ;
Salomon, Robert N. ;
Van Etten, Richard A. ;
Alroy, Joseph ;
Durand, Jean-Bernard ;
Force, Thomas .
NATURE MEDICINE, 2006, 12 (08) :908-916
[23]   Multiplexed protein measurement: technologies and applications of protein and antibody arrays [J].
Kingsmore, SF .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (04) :310-320
[24]   In vivo protein-protein and protein-DNA crosslinking for genomewide binding microarray [J].
Kurdistani, SK ;
Grunstein, M .
METHODS, 2003, 31 (01) :90-95
[25]   Transcriptional regulatory networks in Saccharomyces cerevisiae [J].
Lee, TI ;
Rinaldi, NJ ;
Robert, F ;
Odom, DT ;
Bar-Joseph, Z ;
Gerber, GK ;
Hannett, NM ;
Harbison, CT ;
Thompson, CM ;
Simon, I ;
Zeitlinger, J ;
Jennings, EG ;
Murray, HL ;
Gordon, DB ;
Ren, B ;
Wyrick, JJ ;
Tagne, JB ;
Volkert, TL ;
Fraenkel, E ;
Gifford, DK ;
Young, RA .
SCIENCE, 2002, 298 (5594) :799-804
[26]   Genome-wide protein interaction maps using two-hybrid systems [J].
Legrain, P ;
Selig, L .
FEBS LETTERS, 2000, 480 (01) :32-36
[27]   Response rate of fibrosarcoma cells to cytotoxic drugs on the expression level correlates to the therapeutic response rate of fibrosarcomas and is mediated by regulation of apoptotic pathways [J].
Lehnhardt, M ;
Klein-Hitpass, LK ;
Kuhnen, C ;
Homann, HH ;
Daigeler, A ;
Steinau, HU ;
Roehrs, S ;
Schnoor, L ;
Steinstraesser, L ;
Mueller, O .
BMC CANCER, 2005, 5 (1)
[28]   Expression monitoring by hybridization to high-density oligonucleotide arrays [J].
Lockhart, DJ ;
Dong, HL ;
Byrne, MC ;
Follettie, MT ;
Gallo, MV ;
Chee, MS ;
Mittmann, M ;
Wang, CW ;
Kobayashi, M ;
Horton, H ;
Brown, EL .
NATURE BIOTECHNOLOGY, 1996, 14 (13) :1675-1680
[29]   TYROSINE KINASE-ACTIVITY AND TRANSFORMATION POTENCY OF BCR-ABL ONCOGENE PRODUCTS [J].
LUGO, TG ;
PENDERGAST, AM ;
MULLER, AJ ;
WITTE, ON .
SCIENCE, 1990, 247 (4946) :1079-1082
[30]   High-throughput microarray-based enzyme-linked immunosorbent assay (ELISA) [J].
Mendoza, LG ;
McQuary, P ;
Mongan, A ;
Gangadharan, R ;
Brignac, S ;
Eggers, M .
BIOTECHNIQUES, 1999, 27 (04) :778-+