LIMKi 3
LIMKi 3 is a novel small molecule inhibitor of LIMK1 and LIMK2 with IC50 values of 7 and 8 nM, respectively [1].
LIM kinase (LIMK) includes LIMK1 and LIMK2, which regulate the actin polymerization mediated by the Rho family (Rho, Rac, and Cdc42) and the actin cytoskeleton by phosphorylating and inactivating the cofilin family of actin-depolymerizing factors. The functions of LIMK contribute to its irreplaceable effects in cell movement, division and structure formation[1] [3].
In vitro: In human breast cancer cells MDA-MB-231, treatment with LIMKi 3 (0~10 μM) resulted in the inhibition of LIMK activity and cofilin phosphorylation in a dose-dependent manner, induced a reduction in F-actin signal intensity and serum-stimulated SRF activity. LIMK inhibition also reduced matrigel invasion in three-dimensional invasion assays, but had no effect on microtubule number or organization and wound healing. Although motility was unaffected, LIMK inhibition by LIMKi 3 impaired matrix protein degradation[2].
References:
[1] Ross-Macdonald P, De S H, Guo Q, et al. Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors.[J]. Molecular Cancer Therapeutics, 2008, 7(11):3490-3498.
[2] Scott R W, Hooper S, Crighton D, et al. LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells.[J]. Journal of Cell Biology, 2010, 191(1):169-85.
[3] Jia R X, Duan X, Song S J, et al. LIMK1/2 inhibitor LIMKi 3 suppresses porcine oocyte maturation[J]. Peerj, 2016, 2016(10).
| Physical Appearance | A crystalline solid |
| Storage | Store at -20°C |
| M.Wt | 431.29 |
| Cas No. | 1338247-35-0 |
| Formula | C17H14Cl2F2N4OS |
| Solubility | ≥44.6 mg/mL in DMSO; ≥6.26 mg/mL in EtOH with ultrasonic; insoluble in H2O |
| Chemical Name | N-(5-(1-(2,6-dichlorophenyl)-3-(difluoromethyl)-1H-pyrazol-5-yl)thiazol-2-yl)isobutyramide |
| SDF | Download SDF |
| Canonical SMILES | ClC1=[C@@](C(Cl)=CC=C1)[N@@]2N=C(C(F)F)C=C2C3=CN=C(NC(C(C)C)=O)S3 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Human breast cancer cells MDA-MB-231 |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
24 h, 0~10 µM |
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Applications |
In MDA-MB-231 cells, LIMKi 3 potently inhibited LIMK activity, the treatment with LIMKi 3 (0~10 µM) resulted in a dose-dependent inhibition of cofilin phosphorylation, induced a reduction in F-actin signal intensity and serum-stimulated SRF activity. LIMKi 3 had no effect on microtubule number or organization. 3 µM LIMKi 3 significantly inhibited matrigel invasion in the 3D matrigel invasion assay, 0.1~3 µM LIMKi 3 had no effect on wound healing. 10 µM LIMKi 3 significantly reduced the area of gelatin degradation per cell. Although motility was unaffected, LIMK inhibition by LIMKi 3 impaired matrix protein degradation. |
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References: [1] Scott R W, Hooper S, Crighton D, et al. LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells.[J]. Journal of Cell Biology, 2010, 191(1):169-85. | |
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