G6374 is a selective, effective PROTAC degrader for endogenous IRE1 with DC50 of 0.04 uM and Dmax of 93% in AMO1 multiple myeloma (MM) cells.
G6374 induced effective depletion of IRE1 in KMS27 MM cells, which express similarly high IRE1 levels, with a Dmax of 98% and a DC50 of 0.13 μM.
G6374 promotes stable association between IRE1 and VHL, and drives IRE1 degradation.
G6374 selectively inhibits IRE1-dependent cancer-cell proliferation regardless of the underlying dependency mode.
