A selective BMX and BTK inhibitor
BMX-IN-1 is a highly selective and irreversible inhibitor of BMX kinase [1].
BMX, also known as ETK, is a member of Tec family and plays an important role in regulating ischemia-mediated arteriogenesis and lymphangiogenesis. BMX is mainly expressed in arterial endothelia and in myeloid hematopoietic cells and it has been reported that BMX involves in tumor growth [2].
BMX-IN-1 is a potent BMX kinase inhibitor and has an irreversible function on BMX kinase. When tested with prostate cancer cell lines, BMX-IN-1 treatment inhibited the proliferation of Tel-BMX-transformed Ba/F3 cells at lowdose [1].
参考文献:
[1].Liu, F., et al., Discovery of a selective irreversible BMX inhibitor for prostate cancer. ACS Chem Biol, 2013. 8(7): p. 1423-8.
[2].Holopainen, T., et al., Deletion of the endothelial Bmx tyrosine kinase decreases tumor angiogenesis and growth. Cancer Res, 2012. 72(14): p. 3512-21.
| Kinase experiment [1]: | |
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Kinase assay |
The serially diluted BMX-IN-1 was added to the BTK kinase. After 30 min incubation at RT, ATP (final concentration: 20μM) was added and incubated for 20 min at 37°C. The reactions were stopped by addition of 5X sample buffer. Then the phosphorylation of BTK was detected by western-blot using a pBTK Y551 antibody (BD). |
| Cell experiment [1]: | |
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Cell lines |
Ramos cell line |
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Preparation method |
The solubility of this compound in DMSO is >5.3 mg/mL. 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 |
0.3, 1, 3 and 10 uM for 16/24/48 hours. |
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Applications |
In Ramos cell line, BMX-IN-1 significantly inhibited cell cycle progression at G0/G1 in a dose-dependent manner at 24h and strongly induced apoptosis at a concentration of 1 μM at 8h, while with a longer drug exposure (24 hours), a concentration of 300 nM was sufficient to induce apoptosis. |
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参考文献: [1]. Hong Wu, et al. Discovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphoma. ACS Chem Biol. 2014 May 16; 9(5): 1086–1091. | |
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