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MKC-3946
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
MKC-3946图片
CAS NO:1093119-54-0
规格:98%
分子量:380.5
包装与价格:
包装价格(元)
1mg电议
5mg电议
10mg电议
25mg电议

产品介绍
MKC-3946 is an inhibitor of inositol-requiring enzyme 1α (IRE1α).
CAS:1093119-54-0
分子式:C21H20N2O3S
分子量:380.5
纯度:98%
存储:Store at -20°C

Background:

MKC3946 is a potent and soluble IRE1α inhibitor, used for cancer research.


MKC-3946 blocks?XBP1?mRNA splicing and exhibits cytotoxicity against AML cells. MKC-3946 inhibits XBP1S expression induced by tunicamycin (TM) in NB4 cells (B) and AML sample from patients[1]. MKC-3946 prevents the splicing of the XBP1 mRNA in response to ER stress caused by mutant proinsulin production[2]. MKC-3946 is an IRE1α endoribonuclease domain inhibitor that blocks XBP1 mRNA splicing and triggers modest growth inhibition in MM cells. MKC-3946 inhibits XBP1s expression induced by Tm in a dose-dependent manner, but does not affect phosphorylation of IRE1α. MKC-3946 blocks XBP1 splicing and enhances cytotoxicity induced by bortezomib or 17-AAG. MKC-3946 (10μM) enhances ER stress-mediated apoptosis induced by bortezomib or 17-AAG, and enhances cytotoxicity of ER stressors, even in the presence of BMSCs or exogenous IL-6[3].


MKC-3946 (100 mg/kg, i.p.) inhibits XBP1 splicing in a model of ER stress in vivo, associated with significant growth inhibition of MM cells, alone or with bortezomib. MKC-3946 significantly reduces MM tumor growth in the treatment versus control group. Inhibition of XBP1 splicing by MKC-3946 is associated with decreased MM growth in vivo, alone or in combination with bortezomib[3].


参考文献:
[1]. Sun H, et al. Inhibition of IRE1α-driven pro-survival pathways is a promising therapeutic application in acute myeloid leukemia. Oncotarget. 2016 Apr 5;7(14):18736-49.
[2]. Zhang L, et al. IRE1 inhibition perturbs the unfolded protein response in a pancreatic β-cell line expressing mutant proinsulin, but does not sensitize the cells to apoptosis. BMC Cell Biol. 2014 Jul 10;15:29.
[3]. Mimura N, et al. Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma. Blood. 2012 Jun 14;119(24):5772-81.