Synergistic and antagonistic drug combinations depend on network topology.

ABSTRACT: Drug combinations may exhibit synergistic or antagonistic effects. Rational design of synergistic drug combinations remains a challenge despite active experimental and computational efforts. Because drugs manifest their action via their targets, the effects of drug combinations should depend on the interaction of their targets in a network manner. We therefore modeled the effects of drug combinations along with their targets interacting in a network, trying to elucidate the relationships between the network topology involving drug targets and drug combination effects. We used three-node enzymatic networks with various topologies and parameters to study two-drug combinations. These networks can be simplifications of more complex networks involving drug targets, or closely connected target n

SUBMITTER: Yin N 

PROVIDER: S-EPMC3979733 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature