4μ8C

4μ8C is a potent and selective small molecule inhibitor of the **inositol-requiring enzyme 1 alpha (IRE1α)** endoribonuclease (RNase) activity. IRE1α is a key transmembrane protein that senses endoplasmic reticulum (ER) stress and initiates the unfolded protein response (UPR). Upon activation, IRE1α catalyzes the unconventional splicing of XBP1 mRNA into its active form, XBP1s, which regulates the transcription of chaperone genes. 4μ8C acts by binding covalently to the active site lysine (K907) of the IRE1α RNase domain, effectively blocking XBP1 splicing and subsequent UPR signaling. In preclinical research, particularly in hematologic malignancies like **acute myeloid leukemia (AML)** and multiple myeloma, 4μ8C has been shown to reduce cell survival, inhibit colony formation, and enhance the efficacy of other therapeutic agents such as venetoclax. It is widely utilized as a research tool to investigate the role of ER stress pathways in disease pathogenesis.

Other names

8-formyl-7-hydroxy-4-methylcoumarin7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde