BMS-3 - LIM Kinase (LIMK) 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBMS-3Cat. No.: HY-18304CAS No.: 1338247-30-5分式: CHClFNOS分量: 429.27作靶點(diǎn): LIM Kinase (LIMK)作通路: Cell Cycle/DNA Damage儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 30 mg/mL (69.89 mM)* means

2、soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3295 mL 11.6477 mL 23.2954 mL5 mM 0.4659 mL 2.3295 mL 4.6591 mL10 mM 0.2330 mL 1.1648 mL 2.3295 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 BMS-3種效的 LIMK 抑制劑，抑制 LIMK1 和 LIMK2，IC50 分別為 5 nM 和

3、 6 nM。IC50 & Target LIMK1 LIMK25 nM (IC50) 6 nM (IC50)體外研究BMS-3 (Compound 2) causes a dose-dependent reduction in cell count and induces mitotic arrest by1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEincreases in total nuclear DNA intensity and histone H3 phosphorylation after 24 h treatment in A

4、549 humanlung cancer cells. BMS-3 inhibits A549 human lung cancer cells with EC50 value of 154 nM 1. BMS-3 isused to demonstrate the direct participation of LIMK1 in the phosphorylation of Cofilin. Inhibition of p-LIMKwith 1-50 M of BMS-3 results in a dose-dependent decrease of p-Cofilin after 10 mi

5、n incubation incapacitating conditions. As a control, sperm are also incubated for 10 min under non-capacitating conditionswhich result in low levels of p-Cofilin. In the presence of 1 or 50 M of BMS-3, actin polymerization levels aresignificantly lower compared to controls (DMSO). Mouse sperm are i

6、ncubated under capacitating conditionsfor 90 min in the presence or absence of increasing concentrations of p-LIMK inhibitor BMS-3 (0, 1, 10 and50 M). The increasing concentrations of BMS-3 result in a strong decrease on the percentage of sperm thatundergoes acrosomal exocytosis after stimulation wi

7、th 20 M of Progesterone 2.PROTOCOLKinase Assay 1 The protein kinase domains of human LIMK1 and LIMK2 are expressed as glutathione S-transferase fusionproteins using the Bac-to-Bac system in Sf9 cells. Compounds 1 to 6 (e.g., BMS-3) are assayed for inhibitionof LIMK1 and LIMK2 protein kinase activity

8、 by radioactive phosphate incorporation into biotinylated full-lengthhuman destrin. Reactions are done with a concentration series of compound in 25 mM HEPES, 100 mMNaCl, 5 mM MgCl2, 5 mM MnCl2, 1 M total ATP, 83 g/mL biotinylated destrin, 167 ng/mL glutathione S-transferase-LIMK1, or 835 ng/mL glut

9、athione S-transferase-LIMK2 in a total volume of 60 L at roomtemperature for 30 min (LIMK1) or 60 min (LIMK2). Reactions are terminated by addition of 140 L of 20%TCA/100 mM sodium pyrophosphate, and the precipitates are harvested onto GF/C unifilter plates. Theradioactivity incorporated is determin

10、ed using a TopCount after addition of 35 L Microscint scintillation fluid1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Ross-Macdonald P, et al. Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors. Mol Cancer Ther. 2008Nov;7(11):3490-8.2. Romarowski A, et al. PKA-dependent phosphorylation of LIMK1 and Cofilin is essential for mouse sperm acrosomal exocytosis. DevBiol. 2015 Sep 15;405(2):237-49.McePdfHeightCaution: Product has not been