14003-96-4

4μ8C (14003-96-4) is a selective inhibitor of IRE1α ribonuclease (RNase) activity (IC50?= 60 nM). Covalently binds to lysine 907 in the IRE1 endonuclease domain, blocking substrate access to the active site of IRE1α and inactivating both XBP1 splicing and IRE1α-mediated mRNA degradation but not IRE1 kinase activity.1?Inhibits IRE1α in response to hypoxia or other ER stress-inducing agents but has no effect on proliferation or clonogenic survival of hypoxic cells.2?Blocks production of IL-4, IL-5 and IL-13 production in T cells.3?4μ8C prevents the splicing of the XBP1 mRNA in response to ER stress caused by mutant proinsulin production in pancreatic β-cells.4

8-Formyl-4-methylumbelliferone is an inhibitor that blocks substrate access to the active site of IRE1 and selectively inactivates both Xbp1 splicing and IRE1-mediated mRNA degradation.

Cell permeable: yes

Store at -20°C

1) Cross?et al. (2012),?The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule; Proc. Natl. Acad. Sci. USA,?109?E869 2) Cojocari?et al. (2013),?New small molecule inhibitors of UPR activation demonstrate that PERK, but not IRE1α signaling is essential for promoting adaptation and survival to hypoxia;? Radiother. Oncol.,?108?541 3) Kemp?et al. (2013),?The serine-threonine kinase inositol-requiring enzyme 1α (IRE1α) promotes IL-4 production in T helper cells; J. Biol. Chem.,?288?33272 4) Zhang?et al. (2014),?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.,?15?29