Fig. 5

Drug interactions of rapamycin and lovastatin on days two (N = 7) and three (N = 5), indicating profound synergy between the two agents. The single agent dose-response curve for rapamycin is shown for day two (a) and day three (d). Note that the EC₅₀ more than triples on day three. b. Rapamycin combined with lovastatin has substantial efficacy over much of the dose-response concentration space on day two. e. The dose-response space is similar on day three, despite the shift in the single agent dose-response curve for rapamycin (see d). The Loewe synergy level matrices on day two (c) and day three (f) are similar but with an even greater extent of statistically significant synergy at the later time point. The presence of strong antagonism, antipodal to the synergistic interactions, resulted in a modest global SUM_SYN_ANT score on day two (Fig. 1a) but the global metric reverses on day 3 (Fig. 1b) because of the expanding synergism and weakening antagonism (f)