T5601640

T56-LIMKi efficiently inhibits the growth of ST88-14, U87, Panc-1 cells, A549 lung cancer cells with IC ₅₀ values of 18.3, 7.4, 35.2 and 90 μM, respectively. T56-LIMKi decreases phosphorylated cofilin (p-cofilin) levels and thus inhibits growth of several cancerous cell lines, including those of pancreatic cancer, glioma and schwannoma. It blocks the phosphorylation of cofilin which leads to actin severance and inhibition of tumor cell migration, tumor cell growth, and anchorage-independent colony formation in soft agar. T56-LIMKi (10-50 μM) reduces p-cofilin in a dose-dependent manner in NF1 ^−/− MEFs with an IC ₅₀ of 30 μM. Notably, the inhibitor does not affect the amounts of total cofil. 50μM T56-LIMKi causes a statistically significant reduction in the number of cells exhibiting stress fibers.

T56-LIMKi can induce inhibition of cofilin phosphorylation and Panc-1 tumor shrinkage in vivo . Mice treated with T56-LIMKi (60 mg/kg) shows a significant decrease in tumor volume compared to control.