LIMK1 and LIMK2 regulate the actin cytoskeleton by phosphorylating and inactivating the cofilin family of actin-depolymerizing factors; LIMK1 also acts to destabilize microtubules and regulates cell motility, including tumor metastasis[3]. BMS-5 is a potent LIMK inhibitor with IC50s of 7 nM and 8 nM for LIMK1 and LIMK2, respectively[3]. BMS-5 inhibits cofilin-Ser3 phosphorylation in a dose-dependent manner in Nf2ΔEx2 mouse Schwann cells (MSCs) with an IC50 of ~2 µM, and it reduces Nf2ΔEx2 MSC viability in a dose-dependent manner with an IC50 of 3.9 µM, but does not significantly reduce the viability of control Nf2flox2/flox2 MSCs at equivalent BMS-5 concentrations. At 10 µM BMS-5, Nf2ΔEx2 MSC viability is 40% compared to 83% for controls[4]. BMS-5 (20 or 200 μM/side) or vehicle is bilaterally infused into the hippocampus of rats immediately after contextual fear conditioning training. Rats are tested for memory consolidation 48 h after fear conditioning. Post hoc analysis shows that the group treated with 200 μM BMS-5 expresses lower freezing levels compared to the 20 μM and vehicle groups (P < 0.01). An additional experiment is performed in order to test if a short-term fear memory (STM) could be affected by LIMK inhibition. Animals are infused with 200 μM BMS-5 immediately after training and are tested in the same context 2 h later. No significant difference is found between both groups, BMS-5 and vehicle, in the test, suggesting that actin dynamics briefly after training is not crucial to STM expression[5].
BMS-5 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Nf2ΔEx2 mouse Schwann cells
5 µM
7 h
Treatment with 5 µM BMS-5 resulted in accumulation of Nf2ΔEx2 MSCs in the G2/M phase, increasing the proportion from 20% to 42%.
Oncogene. 2014 Jul 3;33(27):3571-82
Nf2ΔEx2 mouse Schwann cells
3.9 µM
24 h
BMS-5 reduced Nf2ΔEx2 MSC viability in a dose-dependent manner with an IC50 of 3.9 µM, but did not significantly affect the viability of control Nf2flox2/flox2 MSCs at equivalent concentrations.
Oncogene. 2014 Jul 3;33(27):3571-82
Nf2ΔEx2 mouse Schwann cells
2 µM
30 min
BMS-5 inhibited cofilin-Ser3 phosphorylation in a dose-dependent manner in Nf2ΔEx2 MSCs with an IC50 of ~2 µM.
Oncogene. 2014 Jul 3;33(27):3571-82
human neurons derived from sporadic Alzheimer's disease patients
1 μM
from day 7 to the end
To investigate the effect of LIMK1 inhibition on neuronal morphology, results showed no further worsening of neurite length
Alzheimers Res Ther. 2024 Dec 19;16(1):267
human neurons derived from healthy subjects
1 μM
from day 7 to the end
To investigate the effect of LIMK1 inhibition on neuronal morphology, results showed reduced neurite length
Alzheimers Res Ther. 2024 Dec 19;16(1):267
rod photoreceptor cells
10 μM
7 h
Stabilizes actin filaments, preventing their depolymerization during axon retraction
Invest Ophthalmol Vis Sci. 2019 May 1;60(6):2274-2285
rod photoreceptor cells
10 μM
15 min
Inhibits LIMK activity, reduces the production of actin barbed ends, thereby decreasing actin filament severing in the axonal region of rod photoreceptors
Invest Ophthalmol Vis Sci. 2019 May 1;60(6):2274-2285
rod photoreceptor cells
1-30 μM
7 h
Inhibition of LIMK significantly reduced axonal retraction in rod photoreceptor cells.
Invest Ophthalmol Vis Sci. 2015 Dec;56(13):7847-58
mouse embryo cells
200 μM and 400 μM
Inhibition of LIMK1/2 activity caused failure of early embryo cleavage and defects in blastocyst formation
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