G-1749 is a potent, very kinase-selective and allosteric activator of IRE1 RNase activity with EC50 of 9 nM in RNase biochemical assay.
only 6 of 218 other kinases besides IRE1 by more than 50% at 1 uM.
G-1749 occupies a pocket proximal to the DFG motif.
G-1749 significantly increased the cellular levels of XBP1s mRNA and decreased those of DGAT2 in KMS-11 multiple myeloma cells.
G-1749 allosterically inhibits the RNase activity of phosphorylated IRE1
G-1749 stimulates the RNase activity of unphosphorylated IRE1 (IRE1-0P), yet inhibits IRE1-3P.
