Systems Pharmacology and Rational Polypharmacy: Nitric Oxide−Cyclic GMP Signaling Pathway as an Illustrative Example and Derivation of the General Case
Fig 5
Pairwise perturbation of optimal rate constants increased cGMP levels beyond that predicted by the Bliss model.
Comparison of cGMP levels after individual and pairwise perturbation of (A) k1 + k3, (B) k1 + k10, and (C) k3 + k10 with the Bliss model [generated using the perturbation of corresponding individual rate constants and applying eq (15) in the Supplement]. Single perturbations were used to predict paired perturbation signatures. The simulated combination produced cGMP levels that were greater than those predicted by the Bliss model.