BMS-3 is a potent LIMK inhibitor with IC50s of 5 nM and 6 nM for LIMK1 and LIMK2, respectively.
BMS-3 (Compound 2) causes a dose-dependent reduction in cell count and induces mitotic arrest by increases in total nuclear DNA intensity and histone H3 phosphorylation after 24 h treatment in A549 human lung cancer cells. BMS-3 inhibits A549 human lung cancer cells with EC50 value of 154 nM[1]. BMS-3 is used to demonstrate the direct participation of LIMK1 in the phosphorylation of Cofilin. Inhibition of p-LIMK with 1-50 uM of BMS-3 results in a dose-dependent decrease of p-Cofilin after 10 min incubation in capacitating conditions. As a control, sperm are also incubated for 10 min under non-capacitating conditions which result in low levels of p-Cofilin. In the presence of 1 or 50 uM of BMS-3, actin polymerization levels are significantly lower compared to controls (DMSO). Mouse sperm are incubated under capacitating conditions for 90 min in the presence or absence of increasing concentrations of p-LIMK inhibitor BMS-3 (0, 1, 10 and 50 uM). The increasing concentrations of BMS-3 result in a strong decrease on the percentage of sperm that undergoes acrosomal exocytosis after stimulation with 20 uM of Progesterone[2].
References:
[1]. Ross-Macdonald P, et al. Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors. Mol Cancer Ther. 2008 Nov;7(11):3490-8.
[2]. Romarowski A, et al. PKA-dependent phosphorylation of LIMK1 and Cofilin is essential for mouse sperm acrosomal exocytosis. Dev Biol. 2015 Sep 15;405(2):237-49.