Network-level multiple targets

Network-level multiple targets refers to a therapeutic strategy in network pharmacology where a drug or combination of drugs is designed to interact with multiple nodes within a biological pathway or across interconnected networks (Hopkins, A. L., 2008, Nature Chemical Biology). Unlike the traditional "one drug, one target" paradigm, this approach recognizes that complex diseases like cancer or neurodegeneration are driven by robust, redundant biological systems that can bypass the inhibition of a single protein (Kuzmanov, U., & Emili, A., 2013, Genome Medicine). By targeting multiple enzymes, receptors, or signaling molecules simultaneously, network-level interventions aim to disrupt the disease state more effectively while minimizing the emergence of resistance (Csermely, P., et al., 2013, Pharmacology & Therapeutics). This concept is central to polypharmacology and the development of multi-kinase inhibitors or multi-receptor ligands. The goal is to achieve a systemic shift in the biological network's behavior rather than just blocking a single isolated function (Zhang, W., et al., 2019, Briefings in Bioinformatics). While this strategy can enhance efficacy, it also presents challenges in predicting off-target effects and managing the complexity of drug-protein interaction networks (Berger, S. I., & Iyengar, R., 2009, BMC Biology). It is often employed in the treatment of multifactorial conditions where a single-target approach has historically failed to provide durable clinical benefits.

Other names

Network pharmacologyPolypharmacologyMulti-target drug discoverySystems-level targetingMulti-target ligands

Simultaneous modulation of multiple nodes within a biological network to achieve a synergistic therapeutic effect and overcome redundancy or resistance (Hopkins, A. L., 2008, Nature Chemical Biology).