Figure 1.

The relationship between target connectivity and synergy for paired inhibitors. The underlying connectivity for two inhibitors A and B is shown schematically along with intuitive expectations for their combined effect and the simulated dose-dependent response surfaces. (A) If their targets are serial in a pathway, A and B should help each other reduce production. If they inhibit parallel pathways (B, C), the combination effect ought to reflect the rate-limiting reaction for required (‘AND') junctions but should be very synergistic for alternative (‘OR') pathways. (D) More complex network topologies without an intuitive expectation can still be simulated. Lehár et al (2007) sought to categorize and link the set of possible response surfaces to underlying network connectivity (Figure courtesy of J Lehár).