ArticlePLoS computational biology2007
Dynamic simulations on the arachidonic acid metabolic network.
Article in PLoS computational biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 117 citations in OpenAlex.
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- Screening drug target combinations in disease-related molecular networks.BMC bioinformatics · 2019Article
- Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Study on Metabolic Trajectory of Liver Aging and the Effect of Fufang Zhenzhu Tiaozhi on Aging Mice.Frontiers in pharmacology · 2019Article
- Inhibition of proinflammatory pathways by bioactive fraction of Tinospora cordifolia.Inflammopharmacology · 2018Article
- Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy.Frontiers in pharmacology · 2018Article
- LOX inhibitor HOEC interfered arachidonic acid metabolic flux in collagen-induced arthritis rats.American journal of translational research · 2018Article
- Using quantitative systems pharmacology to evaluate the drug efficacy of COX-2 and 5-LOX inhibitors in therapeutic situations.NPJ systems biology and applications · 2018Article
- Predicting Drug Combination Index and Simulating the Network-Regulation Dynamics by Mathematical Modeling of Drug-Targeted EGFR-ERK Signaling Pathway.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug molecules not only interact with specific targets, but also alter the state and function of the associated biological network. How to design drugs and evaluate their functions at the systems level becomes a key issue in highly efficient and low-side-effect drug design. The arachidonic acid metabolic network is the network that produces inflammatory mediators, in which several enzymes, including cyclooxygenase-2 (COX-2), have been used as targets for anti-inflammatory drugs. However, neither the century-old nonsteriodal anti-inflammatory drugs nor the recently revocatory Vioxx have provided completely successful anti-inflammatory treatment. To gain more insights into the anti-inflammatory drug design, the authors have studied the dynamic properties of arachidonic acid (AA) metabolic network in human polymorphous leukocytes. Metabolic flux, exogenous AA effects, and drug efficacy have been analyzed using ordinary differential equations. The flux balance in the AA network was found to be important for efficient and safe drug design. When only the 5-lipoxygenase (5-LOX) inhibitor was used, the flux of the COX-2 pathway was increased significantly, showing that a single functional inhibitor cannot effectively control the production of inflammatory mediators. When both COX-2 and 5-LOX were blocked, the production of inflammatory mediators could be completely shut off. The authors have also investigated the differences between a dual-functional COX-2 and 5-LOX inhibitor and a mixture of these two types of inhibitors. Their work provides an example for the integration of systems biology and drug discovery.
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