LIM Kinase Inhibitor I, LIMKi 3 - Calbiochem

General description

A cell-permeable pyrazolylthiazolo-isobutyramide compound that acts as a potent LIM kinase inhibitor (IC₅₀ = 7 and 8 nM against LIMK1 and LIMK2, respectively) and effectively suppresses cellular cofilin phosphorylation (IC50 ~ 1 µM in A549 and MDA-MB-231 cultures) without affecting tubulin polymerization or inducing cytotoxicity (EC₅₀ >10 µM in A549 proliferation & colony formation assays). Shown to effectively destabilize F-actin structure in MDA-MB-231 breast cancer cells (3 to 10 µM) with concomitant blockage of invasion (by 93% at 10 µM).

A cell-permeable pyrazolylthiazolo-isobutyramide compound that acts as a potent LIM kinase inhibitor (IC₅₀ = 7 and 8 nM against LIMK1 and LIMK2, respectively) and effectively suppresses cellular cofilin phosphorylation (IC₅₀ ~ 1 µM in A549 and MDA-MB-231 cultures) without affecting tubulin polymerization or inducing cytotoxicity (EC₅₀ >10 µM in A549 proliferation and colony formation assays). Shown to effectively destabilize F-actin structure in MDA-MB-231 breast cancer cells (3 to 10 µM) with concomitant blockage of invadopedia-mediated ECM degradation (13% and 10% of control, respectively, by 3 and 10 µM inhibitor) and invasion (45% and 7% of control invasion rate, respectively, by 3 and 10 µM inhibitor). Although reported to exhibit affinity toward AMPKα1 and AMPKα2 in T7 phage-based competition binding studies, inhibitory activity of LIMKi 3 against AMPKα1/2 is not yet directly demonstrated.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
LIMK1 and LIMK2

Reversible: yes

Secondary Target
AMPKA1, AMPKA2, DDR1, PAK3, DCAMKL2

Target IC₅₀: 7 and 8 nM against LIMK1 and LIMK2, respectively

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Scott, R.W., et al. 2010. J. Cell. Biol.191, 169.

Ross-Macdonald, P., et al. 2008. Mol. Cancer Ther.7, 3490.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany