BAMB-4 (ITPKA-IN-C14) 是一种特异性且可透过膜的 ITPKA 抑制剂。 BAMB-4 具有很高的稳定性和膜通透性，并能对抗 1,4,5-三磷酸肌醇 (ITPKA) 的 1,4,5-三磷酸肌醇 (InsP3) 激酶活性，IC50 值为 20微米。 BAMB-4可用于肺癌转移的研究。
BAMB-4 is an inhibitor of inositol-1,4,5-trisphosphate-3-kinase A (ITPKA) with an IC50 value of 20 μM [1].
ITPKA is an InsP3 kinase. It binds to actin filaments and bundles them. This protein regulates actin dynamics as well as inositol phosphate signaling [1].
BAMB-4 was almost completely taken up by H1299 cells. BAMB-4 did not belong to typical kinase inhibitors. Its relatively high specificity and high cellular uptake provide the possibility to effectively inhibit InsP3 kinase in vivo. Among InsP3Kinase inhibitors, BAMB-4 exhibit the lowest inhibition frequency. BAMB-4 showed an inhibitory effect only in 1 from 42 tested targets. There was no detected BAMB-4 target in kinase screens. These results indicated that BAMB-4 is not a typical kinase inhibitor. In vitro, data showed that BAMB-4 increased Km and reduced Vmax with respect to InsP3. BAMB-4 at the lowest concentration (10 μM) increased the Km-value for InsP3 by 160%. BAMB-4 at elevated concentrations did not further rise the Km-value for InsP3. BAMB-4 dose-dependently decreased Vmax from 75% to 50%. Decreased Vmax and increased Km in presence of inhibitor indicated that BAMB-4 might belong to mixed type inhibitors. Data showed that BAMB-4 also reduced Vmax and increased Km with respect to ATP [2].
There is still no any available result of the application of BAMB-4 in animals.
参考文献:
[1].? Schrder D, Tdter K, Gonzalez B, et al. The new InsP 3 Kinase inhibitor BIP-4 is competitive to InsP 3 and blocks proliferation and adhesion of lung cancer cells. Biochemical pharmacology, 2015, 96(2): 143-150.
[2].? Schrder D, Rehbach C, Seyffarth C, et al. Identification of a new membrane-permeable inhibitor against inositol-1, 4, 5-trisphosphate-3-kinase A. Biochemical and biophysical research communications, 2013, 439(2): 228-234.
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