Fig. 2

Calibration of the model by the available data in the literature. Global optimization using a pattern search algorithm was used to optimize all the model parameters using a consistent set of published data plotted here. a Primary data used for parameterization were obtained from the work of D’Alessandro et al.,³³ who measured phosphorylation of Met, Akt, MEK (mitogen-activated protein kinase kinase), ERK (extracellular-regulated kinase) and RSK in vitro in primary mouse hepatocytes at multiple timepoints under treatment with hepatocyte growth factor (HGF) alone or in combination with various inhibitors (experimental data shown as mean ± SD, n = 3). Monte Carlo resampling technique was used to resample the experimental data and recalibrate the model to generate the confidence intervals of the model (modeling data is shown as baseline case and 95% range of the fitted simulations). b Phosphorylated Met (pMet) was also fitted to the experimental data from D’Alessandro et al.³³ (experimental data are shown as mean ± SD, n = 3). c Additionally, phosphorylation of Met, Akt, and ERK were measured in our laboratory³⁰ in HepG2 (human hepatocellular carcinoma cell line) after treatment with various doses of AXT050 peptide (experimental data are shown as mean ± SD, n = 3)