MKC3946 {[allProObj[0].p_purity_real_show]}

MKC3946 质控信息

MKC3946 生物活性

描述

MKC-3946 is IRE1α endoribonuclease domain inhibitor. It inhibited basal XBP1 splicing in RPMI 8226 cells treated with tunicamycin dose-dependently at concentration<10μM post 3h, but did not affect phosphorylation of Ire1α. Consistent with downstream the inhibition of XBP1 splicing by MKC-3946, the expression of XBP1 target genes, SEC61A1, p58IPK, and ERdj4, were decreased. MKC-3946 triggered modest growth inhibition in MM cell lines and significantly enhanced cytotoxicity induced by bortezomib or 17-AAG, even in the presence of bone marrow stromal cells or exogenous IL-6. The ER stress induction by bortezomib and 17-AAG could be blocked by MKC-3946. Apoptosis induced by these agents was enhanced by MKC-3946, associated with increased CHOP. Administration of MKC-3946 at dose of 50mg/kg, i.p., inhibited XBP1 splicing in a model of ER stress induced by tunicamycin in vivo. Daily administration of MKC-3946 at dose of 100mg/kg, i.p., inhibited tumor growth in SCID mice xenograft RPMI 8226 cells and improved the survival level of the mice. Combination of MKC3946 with bortezomib could potentiated these efficiency[2].

MKC3946 细胞实验

Cell Line MCF-7:5C Vascular Smooth Muscle Cells (VSMCs) 1.1B4 cells Mouse bone marrow mesenchymal stem cells MC3T3-E1 cells	Concentration	Treated Time	Description	References
MCF-7:5C	20 μM	72 h	Inhibition of IRE1α:XBP1s UPR pathway enhances TTC-352-induced apoptosis	Mol Cancer Ther. 2021 Jan;20(1):11-25.
Vascular Smooth Muscle Cells (VSMCs)	40 μM	12 h	MKC-3946 significantly reduced the expression of XBP1s, CHOP, ATF6, and ATF4 induced by Ang II, without affecting the expression levels of IRE1α and p-IRE1α.	Int J Biol Sci. 2022 Jan 1;18(3):1053-1064.
1.1B4 cells	10 µM	24 h	MKC3946 treatment significantly inhibited ER stress-induced hIAPP expression and improved β-cell function.	Genes Dis. 2023 Oct 19;11(5):101148.
Mouse bone marrow mesenchymal stem cells	10 nM	24 h	Inhibition of Xbp1s formation significantly decreased the expression of osteoblastic differentiation-related molecules induced by bortezomib	Stem Cell Res Ther. 2020 Nov 30;11(1):516.
MC3T3-E1 cells	10 nM	24 h	Inhibition of Xbp1s formation significantly decreased the expression of osteoblastic differentiation-related molecules induced by bortezomib	Stem Cell Res Ther. 2020 Nov 30;11(1):516.
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MKC3946 动物实验

Species Mice C57BL/KaLwRij mice	Animal Model Aortic Dissection Model Five-week old C57BL/KaLwRij mice	Administration	Dosage	Frequency	Description	References
Mice	Aortic Dissection Model	Intraperitoneal injection	100 mg/kg	Once daily for 2 weeks	MKC-3946 significantly alleviated Ang II-induced aortic dissection formation and medial layer destruction, and reduced ROS production and apoptosis in the aortic wall.	Int J Biol Sci. 2022 Jan 1;18(3):1053-1064.
C57BL/KaLwRij mice	Five-week old C57BL/KaLwRij mice	Intraperitoneal injection	100 mg/kg	Once daily for 7 days	Inhibition of Xbp1s signaling significantly abolished bortezomib-mediated bone formation	Stem Cell Res Ther. 2020 Nov 30;11(1):516.
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MKC3946 动物研究

Dose	Mice: 100 mg/kg[2] (i.p.)
Administration	i.p.

MKC3946 参考文献

MKC3946 实验方案

计算器	摩尔计算器 总药量计算器 工作液计算器
存储液制备		1mg	5mg	10mg
	1 mM 5 mM 10 mM	2.63mL 0.53mL 0.26mL	13.14mL 2.63mL 1.31mL	26.28mL 5.26mL 2.63mL

MKC3946 技术信息