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Systems‐based understanding of pharmacological responses with combinations of multidisciplinary methodologies
Author(s) -
Kariya Yoshiaki,
Honma Masashi,
Suzuki Hiroshi
Publication year - 2013
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.1865
Subject(s) - abstraction , scope (computer science) , computer science , function (biology) , computational biology , systems pharmacology , drug discovery , biological network , molecular pharmacology , systems biology , multidisciplinary approach , biochemical engineering , artificial intelligence , chemistry , bioinformatics , biology , drug , pharmacology , programming language , biochemistry , philosophy , receptor , social science , epistemology , evolutionary biology , sociology , engineering
ABSTRACT The importance of systems‐based pharmacological approaches to drug discovery and development has increasingly been recognized. This reviews summarizes recent advances in the development of systems pharmacology and introduces the methods used for analysis. To understand the cellular response at the molecular level, pathway maps must be prepared to show how the function of the constituent molecules within cells are linked and integrated to form molecular networks. First, the methods used to prepare these pathway maps, such as databases, knowledge bases and software platforms, are introduced. Then the mathematical theories used to analyse the behavior of molecular networks are summarized. To quantitatively predict cellular responses, simulations are performed that are based on the rate equations for each reaction within the pathway map. If the number of reactions described in the pathway map is small, and if the parameter values for the rate constants are available, it is possible accurately to simulate the behavior of the molecular networks. However, to analyse complex maps, mathematical abstraction is required. Such abstraction methods are important to integrate cellular responses and to understand tissue/organ and in vivo pharmacological/toxicological responses. The scope and limitations of the methods are also discussed. Copyright © 2013 John Wiley & Sons, Ltd.