TY - JOUR
T1 - Drug discovery in a multidimensional world
T2 - Systems, patterns, and networks
AU - Dudley, Joel T.
AU - Schadt, Eric
AU - Sirota, Marina
AU - Butte, Atul J.
AU - Ashley, Euan
PY - 2010/10
Y1 - 2010/10
N2 - Despite great strides in revealing and understanding the physiological and molecular bases of cardiovascular disease, efforts to translate this understanding into needed therapeutic interventions continue to lag far behind the initial discoveries. Although pharmaceutical companies continue to increase investments into research and development, the number of drugs gaining federal approval is in decline. Many factors underlie these trends, and a vast number of technological and scientific innovations are being sought through efforts to reinvigorate drug discovery pipelines. Recent advances in molecular profiling technologies and development of sophisticated computational approaches for analyzing these data are providing new, systems-oriented approaches towards drug discovery. Unlike the traditional approach to drug discovery which is typified by a one-drug-one-target mindset, systems-oriented approaches to drug discovery leverage the parallelism and high-dimensionality of the molecular data to construct more comprehensive molecular models that aim to model broader bimolecular systems. These models offer a means to explore complex molecular states (e.g., disease) where thousands to millions of molecular entities comprising multiple molecular data types (e.g., proteomics and gene expression) can be evaluated simultaneously as components of a cohesive biomolecular system. In this paper, we discuss emerging approaches towards systems-oriented drug discovery and contrast these efforts with the traditional, unidimensional approach to drug discovery. We also highlight several applications of these system-oriented approaches across various aspects of drug discovery, including target discovery, drug repositioning and drug toxicity. When available, specific applications to cardiovascular drug discovery are highlighted and discussed.
AB - Despite great strides in revealing and understanding the physiological and molecular bases of cardiovascular disease, efforts to translate this understanding into needed therapeutic interventions continue to lag far behind the initial discoveries. Although pharmaceutical companies continue to increase investments into research and development, the number of drugs gaining federal approval is in decline. Many factors underlie these trends, and a vast number of technological and scientific innovations are being sought through efforts to reinvigorate drug discovery pipelines. Recent advances in molecular profiling technologies and development of sophisticated computational approaches for analyzing these data are providing new, systems-oriented approaches towards drug discovery. Unlike the traditional approach to drug discovery which is typified by a one-drug-one-target mindset, systems-oriented approaches to drug discovery leverage the parallelism and high-dimensionality of the molecular data to construct more comprehensive molecular models that aim to model broader bimolecular systems. These models offer a means to explore complex molecular states (e.g., disease) where thousands to millions of molecular entities comprising multiple molecular data types (e.g., proteomics and gene expression) can be evaluated simultaneously as components of a cohesive biomolecular system. In this paper, we discuss emerging approaches towards systems-oriented drug discovery and contrast these efforts with the traditional, unidimensional approach to drug discovery. We also highlight several applications of these system-oriented approaches across various aspects of drug discovery, including target discovery, drug repositioning and drug toxicity. When available, specific applications to cardiovascular drug discovery are highlighted and discussed.
KW - Drug Discovery
KW - Genomics
KW - Systems Biology
UR - http://www.scopus.com/inward/record.url?scp=77958082168&partnerID=8YFLogxK
U2 - 10.1007/s12265-010-9214-6
DO - 10.1007/s12265-010-9214-6
M3 - Review article
C2 - 20677029
AN - SCOPUS:77958082168
SN - 1937-5387
VL - 3
SP - 438
EP - 447
JO - Journal of Cardiovascular Translational Research
JF - Journal of Cardiovascular Translational Research
IS - 5
ER -