BI09是IRE-1核糖核酸酶的一个抑制剂，其IC50值为1230nM。
B I09 is an IRE-1 RNase inhibitor, with an IC50 of 1230 nM.
B I09 is an IRE-1 RNase inhibitor, with an IC50 of 1230 nM[1]. Treatment of CLL cells with this inhibitor (B I09) mimick XBP-1 deficiency, including upregulation of IRE-1 expression and compromised BCR signaling. B I09 is highly effective in inhibiting splicing of XBP1 mRNA in human WaC3 cells and the expression of XBP-1s in LPS stimulated B cells[2].
B I09 has a halflife of approximately 1.5 hours and reaches its peak concentration of approximately 39 μM in mouse plasma serum 15 minutes after administration. Administration of B I09 to CLL tumor-bearing mice suppress leukemic progression by inducing apoptosis and do not cause systemic toxicity[2].
[1]. Ranatunga S, et al. Synthesis of novel tricyclic chromenone-based inhibitors of IRE-1 RNase activity. J Med Chem. 2014 May 22;57(10):4289-301. [2]. Tang CH, et al. Inhibition of ER stress-associated IRE-1/XBP-1 pathway reduces leukemic cell survival. J Clin Invest. 2014 Jun;124(6):2585-98.
Animal experiment: | Mice[2]Mice are intraperitoneally injected with B I09 (50 mg/kg) on the first 5 days of each week for 3 weeks[2]. |
参考文献: [1]. Ranatunga S, et al. Synthesis of novel tricyclic chromenone-based inhibitors of IRE-1 RNase activity. J Med Chem. 2014 May 22;57(10):4289-301. | |
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