Kinase inhibitors can produce off-target effects and activate linked pathways by retroactivity

BMC Systems Biology

Table 4 Off-target effects can amplify downstream of cycle 2.

	Cycle 2	Cycle 4
Cycles 1-3 with restricted ranges and cycle 4 with default ranges
% Off Target Effects	75.3	35.5
% Off Target Effects with Amplification	--	23.4
% Off Target Effects without Amplification	--	12.1
Cycles 1- 4 with restricted ranges
% Off Target Effects	45.3	67.4
% Off Target Effects with Amplification	--	61.9
% Off Target Effects without Amplification	--	5.5

To test for downstream propagation of off-target effects from cycle 2, the extended n = 3 network was used. If an off-target effect occurred in cycle 4 and the size of the response in cycle 4 exceeded the size of the response in cycle 2, then an off-target effect with amplification was reported for cycle 4. First, the n = 3 restricted parameter space was used for cycles 1 - 3 and the default parameter ranges from Table 1 were used for cycle 4 (Additional File 3 Figure S4H). Next, cycles 2 - 4 were further restricted to ranges which favor off-target effect propagation from cycle 2 to 4 (Additional File 3 Figure S4I). Values listed in the table are percentages out of 5000 randomly selected parameter sets.

ISSN: 1752-0509