Merging Systems Biology with Pharmacodynamics

被引:109
作者
Iyengar, Ravi [1 ]
Zhao, Shan [1 ]
Chung, Seung-Wook [1 ]
Mager, Donald E. [2 ]
Gallo, James M. [1 ]
机构
[1] Mt Sinai Sch Med, Syst Biol Ctr New York, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA
[2] SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA
关键词
PHYSIOLOGICALLY-BASED PHARMACOKINETICS; DRUG DEVELOPMENT; SIGNALING PATHWAYS; NETWORK; PHARMACOLOGY; MODELS;
D O I
10.1126/scitranslmed.3003563
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
The emerging discipline of systems pharmacology aims to combine analysis and computational modeling of cellular regulatory networks with quantitative pharmacology approaches to drive the drug discovery processes, predict rare adverse events, and catalyze the practice of personalized precision medicine. Here, we introduce the concept of enhanced pharmacodynamic (ePD) models, which synergistically combine the desirable features of systems biology and current PD models within the framework of ordinary or partial differential equations. ePD models that analyze regulatory networks involved in drug action can account for a drug's multiple targets and for the effects of genomic, epigenomic, and posttranslational changes on the drug efficacy. This new knowledge can drive drug discovery and shape precision medicine.
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页数:6
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