System biology to assess target relevance in the research and development of molecular inhibitors

What is it about?

This review focuses on how system biology may assist techniques that are used in pharmacological research, such as high-throughput screening, high-throughput analytical characterization of biological samples, preclinical and clinical trials, as well as targets and drug validation in order to reach patients at the lowest possible cost in a translational perspective.

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Why is it important?

In signaling networks, targets can be assessed through topological criteria such as their connectivity and/or centrality. In metabolic networks, the relevance of a target for drug development may rather be assessed through some sort of enzymatic specificity resulting from remote homology, analogy, or specificity in its strict sense. The concept of specificity is especially valuable in the context of a host-parasite relationship where targeting a protein specific of a parasite compared to its host is expected to minimize the noxious collateral effects of the inhibitor to the host. The relevance of putative molecular target must be proven through bench and animal validations prior to going through clinical trials. Flux balance analysis and other modeling methods of system biology enable to assess whether a molecular target can be considered as pathway’s choke or not in a network context, which may facilitate the decision of developing drugs for it.

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