Merck, 5327580001, IRE1α Inhibitor, MKC-3946

General description
A cell-permeable compound that binds to the endoribnuclease domain of IRE1α and inhibits its activity. Blocks XBP1 mRNA splicing in RPMI 8226 human multiple myeloma cells.
A cell-permeable naphthaldehyde derived compound that binds to the endoribnuclease domain of inositol requiring enzyme1α (IRE1α) to inhibit its activity and blocks X-box binding protein 1 (XBP1) mRNA splicing in RPMI 8226 human multiple myeloma (MM) cells. Down-regulates SEC61A1, p58IPK, and ERdj4 genes that are targeted by XBP1. Also shown to block XBP1s expression induced by tunicamycin without affecting the phosphorylation of IRE1a (50 mg/kg, i.p). Shown to enhance bortezomib (Cat. No. 504314) and 17-AAG (Cat. No, 100068) induced toxicity and apoptosis in RPMI8226 and INA6 cells. However, it does not have any significant effect on normal mononuclear cells. Suppresses the growth of RPMI 8226 xenografts in a model of human MM in mice (50 mg/kg, i.p.).

Please note that the molecular weight for this compound is batch-specific due to variable water content.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
IRE1
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Mimura, N., et al. 2012. Blood.119, 5772.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)