We hypothesized that when there is a positive correlation between phospho EGFR and its total level, then effectively reducing both forms of the receptor must be as therapeutically effective as or even more effective than inhibiting ARN-509 clinical trial kinase activity. There is a linear relationship between the whole and phospho EGFR across a majority of patient samples and no relationship with a minor subset of patient samples, where EGFR was expressed at higher-than normal levels, as shown in Figure 6D but phospho EGFR levels were unchanged. The result TE 64562 treatment EGFR phosphorylation was tested as a function of time, although TE 64562 didn’t change EGFR kinase activity in a single timepoint. MDA MB 231 cells were pre treated with TE 64562 for thirty minutes, followed closely by EGF therapy for increasing amounts of time. It was noticed that EGFR remained phosphorylated at 60 minutes Messenger RNA (mRNA) 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 very nearly basal level. TE 64562 inhibits tumefaction development in MDA MB 231 xenograft tumors and increases survival with no observed toxicity. MDA MB 231 xenograft tumors were grown within the subcutaneous flank area of nude mice which were treated bi-weekly with all the TE 64562 peptide, Tat peptide or car, intraperitoneally. The mean cyst size is plotted over time. The asterisks show that the mean size of the TE 64562 treated cancers is statistically different in the Tat and saline treated tumor dimensions at that time point. The amount of rats within endpoints, as defined by tumor size cutoff, tumor ulceration and human anatomy training rating, at each time level are plotted as a Kaplan and Meier survival curve. The median survival, the amount of days at which the portion of rats within endpoints is equal Decitabine clinical trial to 50%, is plotted for every treatment group. The survival curves for the Tat and Saline groups were in comparison to the survival curve for the TE 64562 team and the P value was derived using the log rank test. The asterisks designate an important huge difference using the indicated P values. The mean bodyweight for every treatment group is plotted with time. After 35 days of dosing, areas were obtained and fixed. Representative H&E stained sections from kidney, liver and spleen are found for every treatment group. Results are representative of two independent studies. Also see Figure S4. doi:10. 1371/journal. pone. 0049702. g004 TE 64562 interacts with EGFR and prevents dimerization. SK Deborah MC cells were transfected with the intracellular domain of EGFR or the ICD of EGFR missing the overall 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 cellular lysates with streptavidin coated beads.