We hypothesized that if there is a positive correlation between phospho EGFR and its total level, then effectively reducing both forms of the receptor ought to be as therapeutically effective as or more effective than inhibiting natural product library kinase activity. There is a linear relationship between the whole and phospho EGFR across a majority of patient samples and no relationship with a subset of patient samples, where EGFR was expressed at higher-than normal levels, as shown in Figure 6D but phospho EGFR levels were unchanged. Although TE 64562 did not change EGFR kinase activity at a single timepoint, the result TE 64562 treatment EGFR phosphorylation was examined as a function of time. MDA MB 231 cells were pre-treated with TE 64562 for 30 minutes, followed by EGF therapy for increasing amounts of time. It was noticed that EGFR remained phosphorylated at 60 minutes Plastid EGF treatment in the presence of TE 64562, whereas, without TE 64562 pre treatment, the phosphorylation of EGFR at 60 minutes was paid off to almost basal level. TE 64562 inhibits cyst development in MDA MB 231 xenograft tumors and increases survival without any observed toxicity. MDA MB 231 xenograft tumors were grown in the subcutaneous flank region of nude mice which were treated bi weekly with the TE 64562 peptide, Tat peptide or vehicle, intraperitoneally. The mean tumefaction size is plotted over time. The asterisks indicate that the mean size of the TE 64562 treated tumors is statistically different from the saline and Tat treated tumor styles at that time point. The number of rats within endpoints, as outlined by tumor size cutoff, tumor ulceration and body training rating, at each time point are plotted as a Meier survival curve and Kaplan. The average survival, how many days where the fraction of mice within endpoints is equal supplier Gemcitabine to 50%, is plotted for every treatment group. The survival curves for the Tat and Saline groups were compared to the survival curve for the TE 64562 team and the P value was derived utilizing the log rank test. The asterisks identify an important big difference with the indicated P values. The mean bodyweight for each treatment group is plotted with time. After 35 days of dosing, areas were collected and fixed. Representative H&E stained sections from liver, kidney and spleen are shown for every treatment group. Effects are representative of two independent studies. Also see Figure S4. doi:10. 1371/journal. pone. 0049702. g004 TE 64562 interacts with EGFR and stops dimerization. SK Deborah MC cells were transfected with the intracellular domain of EGFR or the ICD of EGFR lacking the whole JXM region or the JMA region. Biotinylated peptides at a concentration of 0. 1 mM or 0. 5 mM were incubated with SK NMC cells for just two hours and precipitated from mobile lysates with streptavidin coated beads.