T 5601640

T56-LIMKi is a selective inhibitor of LIMK2; inhibits the growth of Panc-1 cells with an IC50 of 35.2 μM.

Signaling Pathways >> Cell Cycle/DNA Damage >> LIM Kinase (LIMK)

Research Areas >> Cancer

LIMK2

T56-LIMKi efficiently inhibits the growth of ST88-14, U87, Panc-1 cells, A549 lung cancer cells with IC50 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[1]. 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 IC50 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[2].

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[1].

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[1].

Mice: T56-LIMKi is dissolved in 0.5% carboxymethylcellulose solution. Mice are implanted with xenografted Panc-1 cells. Treatment is started 7 days later. Mice in the two experimental groups are each treated with a daily oral non-toxic dose of T56-LIMKi (30 or 60 mg/kg in gavage) and mice in the control group receives only the vehicle (0.5% CMC) in the gavage[1].

[1]. Rak R, et al. Novel LIMK2 Inhibitor Blocks Panc-1 Tumor Growth in a mouse xenograft model. Oncoscience. 2014 Jan 1;1(1):39-48. eCollection 2014.

[2]. Mashiach-Farkash E, et al. Computer-based identification of a novel LIMK1/2 inhibitor that synergizes with salirasib to destabilize the actin cytoskeleton. Oncotarget. 2012 Jun;3(6):629-39.

LIMKi 3 | BMS-3