IXA4 是一种高选择性、无毒的 IRE1/XBP1s 激活剂。IXA4 激活IRE1/XBP1s 信号，而没有全局激活未折叠蛋白反应 (UPR) 或其他应激反应信号通路 (例如热休克反应或氧化应激反应)。IXA4 通过激活 IRE1 减少 APP 分泌。
货号:ajcx36360
CAS:1185329-96-7
分子式:C24H28N4O4
分子量：436.5
溶解度:DMSO : 100 mg/mL (229.10 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

IXA4 is a highly selective, non-toxic IRE1/XBP1s activator. IXA4 activates IRE1/XBP1s signaling without globally activating the unfolded protein response (UPR) or other stress-responsive signaling pathways (e.g., the heat shock response or oxidative stress response). IXA4 reduces secretion of APP through IRE1 activation[1].

IXA4 (10 μM; 4 hours) selectively upregulates XBP1s mRNA, relative to genes regulated by ATF6 (e.g., BiP) or PERK (e.g., CHOP), in other cell lines including Huh7 and SHSY5Y cells[1]. IXA4 (10μM; 18 hours) reduces Aβ levels 50% in conditioned media prepared on CHO7PA2 cells expressing the V717F APP (APPV717F) mutant[1]. IXA4 rescues mitochondrial defects in SH-SY5Y cells expressing disease-relevant APP mutants. IXA4 (10μM; 4 hours) promotes adaptive IRE1/XBP1s signaling, but not RIDD, following 4 hrs of treatment in HEK293T cells[1].IXA4 also promotes selective transcriptional remodeling of ER proteostasis pathways, relative to cytosolic or mitochondrial pathways[1].

[1]. Grandjean JMD, et al. Pharmacologic IRE1/XBP1s activation confers targeted ER proteostasis reprogramming. Nat Chem Biol. 2020;16(10):1052-1061.