Applications of metabolomics in drug discovery and development

被引:158
作者
Wishart, David S. [1 ,2 ]
机构
[1] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E8, Canada
[2] Univ Alberta, Dept Comp Sci, Edmonton, AB T6G 2E8, Canada
关键词
D O I
10.2165/00126839-200809050-00002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Metabolomics is a relatively new field of 'omics' technology that is primarily concerned with the global or system-wide characterization of small molecule metabolites using technologies such as nuclear magnetic resonance, liquid chromatography and/or mass spectrometry. Its unique focus on small molecules and the physiological effects of small molecules aligns the field of metabolomics very closely with the aims and interests of many researchers in the pharmaceutical industry. Because of its conceptual and technical overlap with many aspects of pharmaceutical research, metabolomics is now finding applications that span almost the full length of the drug discovery and development pipeline, from lead compound discovery to post-approval drug surveillance. This review explores some of the most interesting or significant applications of metabolomics as they relate to pharmaceutical research and development. Specific examples are given that show how metabolomics can be used to facilitate lead compound discovery, to improve biomarker identification (for monitoring disease status and drug efficacy) and to monitor drug metabolism and toxicity. Other applications are also discussed, including the use of metabolomics to facilitate clinical trial testing and to improve post-approval drug monitoring. These examples show that metabolomics potentially offer drug researchers and drug regulators an effective, inexpensive route to addressing many of the riskier or more expensive issues associated with the discovery, development and monitoring of drug products.
引用
收藏
页码:307 / 322
页数:16
相关论文
共 102 条
[41]   From genomics to chemical genomics: new developments in KEGG [J].
Kanehisa, Minoru ;
Goto, Susumu ;
Hattori, Masahiro ;
Aoki-Kinoshita, Kiyoko F. ;
Itoh, Masumi ;
Kawashima, Shuichi ;
Katayama, Toshiaki ;
Araki, Michihiro ;
Hirakawa, Mika .
NUCLEIC ACIDS RESEARCH, 2006, 34 :D354-D357
[42]   Heteronuclear 19F-1H statistical total correlation spectroscopy as a tool in drug metabolism:: Study of flucloxacillin biotransformation [J].
Keun, Hector C. ;
Athersuch, Toby J. ;
Beckonert, Olaf ;
Wang, Yulan ;
Saric, Jasmina ;
Shockcor, John P. ;
Lindon, John C. ;
Wilson, Ian D. ;
Holmes, Elaine ;
Nicholson, Jeremy K. .
ANALYTICAL CHEMISTRY, 2008, 80 (04) :1073-1079
[43]   Application of metabonomics in drug development [J].
Keun, Hector C. ;
Athersuch, Toby J. .
PHARMACOGENOMICS, 2007, 8 (07) :731-741
[44]   Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry [J].
Kind, Tobias ;
Fiehn, Oliver .
BMC BIOINFORMATICS, 2007, 8 (1)
[45]   Approaches towards the automated interpretation and prediction of electrospray tandem mass spectra of non-peptidic combinatorial compounds [J].
Klagkou, K ;
Pullen, F ;
Harrison, M ;
Organ, A ;
Firth, A ;
Langley, GJ .
RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2003, 17 (11) :1163-1168
[46]   Molecular formula analysis by an MS/MS/MS technique to expedite dereplication of natural products [J].
Konishi, Yasuo ;
Kiyota, Taira ;
Draghici, Cristina ;
Gao, Jin-Ming ;
Yeboah, Faustinus ;
Acoca, Stephane ;
Jarussophon, Suwatchai ;
Purisima, Enrico .
ANALYTICAL CHEMISTRY, 2007, 79 (03) :1187-1197
[47]  
Kristal Bruce S., 2007, V358, P159, DOI 10.1007/978-1-59745-244-1_10
[48]   Discovering the hidden secondary metabolome of Myxococcus xanthus:: a study of intraspecific diversity [J].
Krug, Daniel ;
Zurek, Gabriela ;
Revermann, Ole ;
Vos, Michiel ;
Velicer, Gregory J. ;
Mueller, Rolf .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2008, 74 (10) :3058-3068
[49]   Noninvasive human metabolome analysis for differential diagnosis of inborn errors of metabolism [J].
Kuhara, Tomiko .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2007, 855 (01) :42-50
[50]   Vaidecoxib withdrawal leaves pain relief treatment gap [J].
Lang, L .
GASTROENTEROLOGY, 2005, 128 (07) :1769-1770