IXA6

IXA6 is a novel IRE1/XBP1s activator, and can induce IRE1 RNase activity[1].

Research Areas >> Others

Signaling Pathways >> Cell Cycle/DNA Damage >> IRE1

IXA6 (10 µM; 4 or 18 h) selectively activates IRE1-XBP1s signaling, and activates the XBP1s transcriptional response[1]. IXA6 (10 µM; 4 h) shows selectivity for IRE1-XBP1s-dependent ER proteostasis remodeling[1]. IXA6 (10 µM; 18 h) reduces secretion of APP through IRE1 activation[1]. Western Blot Analysis[1] Cell Line: HEK293T cells Concentration: 10 µM Incubation Time: 18 hours Result: Increasesd in ER proteostasis factor gene expression correspond to increased protein levels. RT-PCR[1] Cell Line: HEK293T cells Concentration: 10 µM Incubation Time: 4 hours Result: Activated the IRE1-XBP1s geneset to levels about 30-40% that observed for Tg (Tg representing 100% activation of each gene). Cell Viability Assay[1] Cell Line: HEK293T cells Concentration: 10 µM Incubation Time: 4 hours Result: Observed high level of overlap (64%) for genes induced by XBP1s and IXA6. RT-PCR[1] Cell Line: Huh7 and SHSY5Y cells Concentration: 10 µM Incubation Time: 4 hours Result: Upregulated XBP1s mRNA selectively, in cell lines including Huh7 and SHSY5Y cells. RT-PCR[1] Cell Line: CHO cells Concentration: 10 µM Incubation Time: 18 hours Result: Observed reduction in Aβ secretion blocked by cotreatment with 4µ8c, confirming this reduction is dependent on IRE1 RNAse activity in CHO7WD10 cells stably expressing wild-type APP (APPWT) and in cells treated with the IXA6.

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