Identification of a Selective Pharmacologic IRE1/XBP1s Activator with Enhanced Tissue Exposure.

ABSTRACT: Activation of the IRE1/XBP1s signaling arm of the unfolded protein response (UPR) has emerged as a promising strategy to mitigate etiologically diverse diseases. Despite this promise, few compounds are available to selectively activate IRE1/XBP1s signaling to probe the biologic and therapeutic implications of this pathway in human disease. Recently, we identified the compound IXA4 as a highly selective activator of protective IRE1/XBP1s signaling. While IXA4 has proven useful for increasing IRE1/XBP1s signaling in cultured cells and mouse liver, the utility of this compound is restricted by its limited activity in other tissues. To broaden our ability to pharmacologically interrogate the impact of IRE1/XBP1s signaling in vivo, we sought to identify IRE1/XBP1s activators with greater

SUBMITTER: Sun J 

PROVIDER: S-EPMC12523807 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature