Figure 4. Pharmacodynamic effects in tumor tissue.
Biopsies were done at the dose level of 180 mg thrice a week. Phosphorylation of cofilin normalized to GAPDH at baseline and at 15 - 28 days of intermittent dosing was assayed using an immuno-chemiluminescence assays and results are presented as percentage of pre-dose levels (A) A reduction of more than 50% of p-cofilin levels were seen in 3/8 patients. (B) Phosphorylation of MLC2 was measured by IHC in pre- and post-treatment tumor specimens of patients treated with AT13148 showing reduction in phosphorylation in only 1/5 samples.