A formal model for analyzing drug combination effects and its application in TNF-α-induced NFκB pathway

BMC Systems Biology

Table 2 Simulation and experimental results for the case study of TNF-α-induced NFκB pathway.

Inhibitor A	Inhibitor B	Synergism Assessment Factor (Simulation)		Predicted interaction	Synergism Assessment Factor (Experiment)
		simplified system	original system
Geldanamycin	Aldehyde	-0.0632	-0.2678	Synergism	-0.0167
Geldanamycin	PS-1145	-0.1248	-0.2555	Synergism	-0.1878
PS-1145	Aldehyde	-0.1754	-0.1754	Synergism	-0.3931

Here we consider the synergism assessment factors of the three combinations in the simplified and original system. The sign of synergism assessment factor indicates whether the drug combination generates synergistic effect or not. If the sign is negative, it is synergistic effect. Otherwise, it is antagonistic effect. In the experiment, ICAM-1 expression is considered as the measurement readout of the efficacy of drugs or drug combinations. We also evaluate the effects of drug combination by calculating synergism assessment factor (see Eq. 3). The negative values represent synergism since we rewrite calculation formula of Bliss independence model according to survival ratio rather than inhibition ratio.

ISSN: 1752-0509